Comprehensive Physiology Wiley Online Library

Physiological and Pathological Angiogenesis in the Adult Pulmonary Circulation

Full Article on Wiley Online Library


Angiogenesis occurs during growth and physiological adaptation in many systemic organs, for example, exercise‐induced skeletal and cardiac muscle hypertrophy, ovulation, and tissue repair. Disordered angiogenesis contributes to chronic inflammatory disease processes and to tumor growth and metastasis. Although it was previously thought that the adult pulmonary circulation was incapable of supporting new vessel growth, over that past 10 years new data have shown that angiogenesis within this circulation occurs both during physiological adaptive processes and as part of the pathogenic mechanisms of lung diseases. Here we review the expression of vascular growth factors in the adult lung, their essential role in pulmonary vascular homeostasis and the changes in their expression that occur in response to physiological challenges and in disease. We consider the evidence for adaptive neovascularization in the pulmonary circulation in response to alveolar hypoxia and during lung growth following pneumonectomy in the adult lung. In addition, we review the role of disordered angiogenesis in specific lung diseases including idiopathic pulmonary fibrosis, acute adult distress syndrome and both primary and metastatic tumors of the lung. Finally, we examine recent experimental data showing that therapeutic enhancement of pulmonary angiogenesis has the potential to treat lung diseases characterized by vessel loss. © 2011 American Physiological Society. Compr Physiol 1:1473‐1508, 2011.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images

Figure 1. Figure 1.

Microscopic images of semithin (1 μ) resin‐embedded sections stained with toluidine blue from alveolar walls of normoxic and hypoxic rat lung following 2 weeks of exposure to hypoxia (Fio2 = 0.10). (Panel A) Image taken from control lung showing numerous capillaries within the alveolar wall. (Panel B) Image of an alveolar wall taken from chronically hypoxic lung tissue. Some capillaries appear to protrude from the alveolar wall into the alveolar lumen, a pattern not seen in control lungs. (Scale bar indicates 10 μm, ×100 objective). Reproduced with permission from Howell et al. .

Figure 2. Figure 2.

Schematic representation of oxygen uptake in a pulmonary alveolus at normal (Panel A) and reduced (Panels B and C) partial pressures of inspired oxygen (PIo2). The plots show partial pressure of oxygen in capillary blood (Pco2) rising progressively toward that of alveolar gas (PAo2) as blood traverses the alveolar capillary. Under resting conditions, RBC transit time in the alveolar capillary is 0.75 s. This reduces during exercise as blood flow velocity increases due to increased cardiac output; a representative value of 0.25 s is used here for illustrative purposes. The partial pressure of oxygen in the blood at the time of entry into the capillary is that of mixed venous blood (Pvo2). Resting values of Pvo2 fall with reducing PIo2; further reductions are seen during exercise but, for simplicity, these are not illustrated here. At normal PIo2, there is a large partial pressure gradient between alveolar gas and mixed venous blood resulting in a rapid rate of diffusion of oxygen across the alveolar capillary membrane so that equilibration is achieved before the capillary blood leaves the alveolus, both at rest and during exercise. With moderate reductions in PIo2, the reduced gradient between the alveolar gas and the mixed venous blood reduces the rate of oxygen transfer but this is still sufficient to allow equilibration at rest. However, with reduced transit time during exercise equilibration is not achieved so oxygen uptake becomes diffusion limited. At the lowest values of PIo2, diffusion limitation is seen both at rest and during exercise. Note all values shown are representative, not exact. The principles illustrated in this schematic are based on data and concepts elucidated by Wagner, West, Weibel, Scheid and colleagues .

Figure 3. Figure 3.

Postmortem angiogram demonstrating extensive neovascularization in a lung from a patient with IPF (right panel) as compared to normal lung (left panel). Photomicrograph kindly provided by Professor Dame Margaret Turner‐Warwick M.D, Ph.D., FRCP and reproduced by permission from Keane et al. (Inflammation injury and Repair. In: Textbook of Respiratory Medicine, edited by Mason R, Broaddus C, Murray J. and Nadel J. Philadelphia: Elsevier, 2005, p. 449‐490).

Figure 1.

Microscopic images of semithin (1 μ) resin‐embedded sections stained with toluidine blue from alveolar walls of normoxic and hypoxic rat lung following 2 weeks of exposure to hypoxia (Fio2 = 0.10). (Panel A) Image taken from control lung showing numerous capillaries within the alveolar wall. (Panel B) Image of an alveolar wall taken from chronically hypoxic lung tissue. Some capillaries appear to protrude from the alveolar wall into the alveolar lumen, a pattern not seen in control lungs. (Scale bar indicates 10 μm, ×100 objective). Reproduced with permission from Howell et al. .

Figure 2.

Schematic representation of oxygen uptake in a pulmonary alveolus at normal (Panel A) and reduced (Panels B and C) partial pressures of inspired oxygen (PIo2). The plots show partial pressure of oxygen in capillary blood (Pco2) rising progressively toward that of alveolar gas (PAo2) as blood traverses the alveolar capillary. Under resting conditions, RBC transit time in the alveolar capillary is 0.75 s. This reduces during exercise as blood flow velocity increases due to increased cardiac output; a representative value of 0.25 s is used here for illustrative purposes. The partial pressure of oxygen in the blood at the time of entry into the capillary is that of mixed venous blood (Pvo2). Resting values of Pvo2 fall with reducing PIo2; further reductions are seen during exercise but, for simplicity, these are not illustrated here. At normal PIo2, there is a large partial pressure gradient between alveolar gas and mixed venous blood resulting in a rapid rate of diffusion of oxygen across the alveolar capillary membrane so that equilibration is achieved before the capillary blood leaves the alveolus, both at rest and during exercise. With moderate reductions in PIo2, the reduced gradient between the alveolar gas and the mixed venous blood reduces the rate of oxygen transfer but this is still sufficient to allow equilibration at rest. However, with reduced transit time during exercise equilibration is not achieved so oxygen uptake becomes diffusion limited. At the lowest values of PIo2, diffusion limitation is seen both at rest and during exercise. Note all values shown are representative, not exact. The principles illustrated in this schematic are based on data and concepts elucidated by Wagner, West, Weibel, Scheid and colleagues .

Figure 3.

Postmortem angiogram demonstrating extensive neovascularization in a lung from a patient with IPF (right panel) as compared to normal lung (left panel). Photomicrograph kindly provided by Professor Dame Margaret Turner‐Warwick M.D, Ph.D., FRCP and reproduced by permission from Keane et al. (Inflammation injury and Repair. In: Textbook of Respiratory Medicine, edited by Mason R, Broaddus C, Murray J. and Nadel J. Philadelphia: Elsevier, 2005, p. 449‐490).

 1. Abdulmalek K, Ashur F, Ezer N, Ye F, Magder S, Hussain SN. Differential expression of Tie‐2 receptors and angiopoietins in response to in vivo hypoxia in rats. Am J Physiol Lung Cell Mol Physiol 281: L582‐L590, 2001.
 2. Abraham D, Taghavi S, Riml P, Paulus P, Hofmann M, Baumann C, Kocher A, Klepetko W, Aharinejad S. VEGF‐A and ‐C but not ‐B mediate increased vascular permeability in preserved lung grafts. Transplantation 73: 1703‐1703, 2002.
 3. Achen MG, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA. Vascular endothelial growth factor D (VEGF‐D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci U S A 95: 548‐548, 1998.
 4. Addison CL, Daniel TO, Burdick MD, Liu H, Ehlert JE, Xue YY, Buechi L, Walz A, Richmond A, Strieter RM. The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR(+) CXC chemokine‐induced angiogenic activity [In Process Citation]. J Immunol 165: 5269‐5269, 2000.
 5. Allen TC, Fudala R, Nash SE, Kurdowska A. Anti‐interleukin 8 autoantibody: Interleukin 8 immune complexes visualized by laser confocal microscopy in injured lung. Arch Pathol Lab Med 131: 452‐452, 2007.
 6. Altorki N, Lane ME, Bauer T, Lee PC, Guarino MJ, Pass H, Felip E, Peylan‐Ramu N, Gurpide A, Grannis FW, Mitchell JD, Tachdjian S, Swann RS, Huff A, Roychowdhury DF, Reeves A, Ottesen LH, Yankelevitz DF. Phase II proof‐of‐concept study of pazopanib monotherapy in treatment‐naive patients with stage I/II resectable non‐small‐cell lung cancer. J Clin Oncol 28: 3131‐3131, 2010.
 7. Alvarez DF, Huang L, King JA, ElZarrad MK, Yoder MC, Stevens T. Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity. Am J Physiol Lung Cell Mol Physiol 294: L419‐L430, 2008.
 8. Anderson L, Lowery JW, Frank DB, Novitskaya T, Jones M, Mortlock DP, Chandler RL, de Caestecker MP. Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension. Am J Physiol Regul Integr Comp Physiol 298: R833‐R842, 2009.
 9. Antoniou KM, Tzouvelekis A, Alexandrakis MG, Sfiridaki K, Tsiligianni I, Rachiotis G, Tzanakis N, Bouros D, Milic‐Emili J, Siafakas NM. Different angiogenic activity in pulmonary sarcoidosis and idiopathic pulmonary fibrosis. Chest 130: 982‐982, 2006.
 10. Antony VB, Hott JW, Godbey SW, Holm K. Angiogenesis in mesotheliomas. Role of mesothelial cell derived IL‐8. Chest 109: 21S‐22S, 1996.
 11. Arcasoy MO. The non‐haematopoietic biological effects of erythropoietin. Br J Haematol 141: 14‐14, 2008.
 12. Arenberg DA, Keane MP, DiGiovine B, Kunkel SL, Morris SB, Xue YY, Burdick MD, Glass MC, Iannettoni MD, Strieter RM. Epithelial‐neutrophil activating peptide (ENA‐78) is an important angiogenic factor in non‐small cell lung cancer. J Clin Invest 102: 465‐465, 1998.
 13. Arenberg DA, Kunkel SL, Polverini PJ, Glass M, Burdick MD, Strieter RM. Inhibition of interleukin‐8 reduces tumorigenesis of human non‐small cell lung cancer in SCID mice. J Clin Invest 97: 2792‐2802, 1996.
 14. Armstrong LC, Bjorkblom B, Hankenson KD, Siadak AW, Stiles CE, Bornstein P. Thrombospondin 2 inhibits microvascular endothelial cell proliferation by a caspase‐independent mechanism. Mol Biol Cell 13: 1893‐1893, 2002.
 15. Asahara T, Murohara T, Sullivan A, Silver M, Van Der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science 275: 964‐964, 1997.
 16. Asikainen TM, Schneider BK, Waleh NS, Clyman RI, Ho WB, Flippin LA, Gunzler V, White CW. Activation of hypoxia‐inducible factors in hyperoxia through prolyl 4‐hydroxylase blockade in cells and explants of primate lung. Proc Natl Acad Sci U S A 102: 10212‐10212, 2005.
 17. Atkinson C, Stewart S, Imamura T, Trembath RC, Morrell NW. Immunolocalisation of BMPR‐II and TGF‐ss type I and II receptors in primary plexogenic pulmonary hypertension. J Heart Lung Transplant 20: 149, 2001.
 18. Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 105: 1672‐1672, 2002.
 19. Augustin HG, Koh GY, Thurston G, Alitalo K. Control of vascular morphogenesis and homeostasis through the angiopoietin‐Tie system. Nat Rev Mol Cell Biol 10: 165‐165, 2009.
 20. Babaei S, Teichert‐Kuliszewska K, Zhang Q, Jones N, Dumont DJ, Stewart DJ. Angiogenic actions of angiopoietin‐1 require endothelium‐derived nitric oxide. Am J Pathol 162: 1927‐1927, 2003.
 21. Bachofen H, Wangensteen D, Weibel ER. Surfaces and volumes of alveolar tissue under zone II and zone III conditions. J Appl Physiol 53: 879‐879, 1982.
 22. Baile EM, Minshall D, Dodek PM, Pare PD. Blood flow to the trachea and bronchi: The pulmonary contribution. J Appl Physiol 76: 2063‐2063, 1994.
 23. Balemans W, Van Hul W. Extracellular regulation of BMP signaling in vertebrates: A cocktail of modulators. Dev Biol 250: 231‐231, 2002.
 24. Bar‐Eli M. Role of interleukin‐8 in tumor growth and metastasis of human melanoma. Pathobiology 67: 12‐12, 1999.
 25. Basnyat B, Murdoch DR. High‐altitude illness. Lancet 361: 1967‐1967, 2003.
 26. Becker PM, Waltenberger J, Yachechko R, Mirzapoiazova T, Sham JS, Lee CG, Elias JA, Verin AD. Neuropilin‐1 regulates vascular endothelial growth factor‐mediated endothelial permeability. Circ Res 96: 1257‐1257, 2005.
 27. Beleslin‐Cokic BB, Cokic VP, Yu X, Weksler BB, Schechter AN, Noguchi CT. Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells. Blood 104: 2073‐2073, 2004.
 28. Belperio JA, Keane MP, Burdick MD, Lynch JP 3rd, Xue YY, Li K, Ross DJ, Strieter RM. Critical role for CXCR3 chemokine biology in the pathogenesis of bronchiolitis obliterans syndrome. J Immunol 169: 1037‐1037, 2002.
 29. Ben‐Baruch A, Michiel DF, Oppenheim JJ. Signals and receptors involved in recruitment of inflammatory cells. J Biol Chem 270: 11703‐11703, 1995.
 30. Beppu H, Ichinose F, Kawai N, Jones RC, Yu PB, Zapol WM, Miyazono K, Li E, Bloch KD. BMPR‐II heterozygous mice have mild pulmonary hypertension and an impaired pulmonary vascular remodeling response to prolonged hypoxia. Am J Physiol Lung Cell Mol Physiol 287: L1241‐L1247, 2004.
 31. Bernard S, Luchtel DL, Polissar N, Hlastala MP, Lakshminarayan S. Structure and size of bronchopulmonary anastomoses in sheep lung. Anat Rec A Discov Mol Cell Evol Biol 286: 804‐804, 2005.
 32. Bikfalvi A, Bicknell R. Recent advances in angiogenesis, anti‐angiogenesis and vascular targeting. Trends Pharmacol Sci 23: 576‐576, 2002.
 33. Bitterman PB. Pathogenesis of fibrosis in acute lung injury. Am J Med 92: 39S‐43S, 1992.
 34. Bolender RP, Hyde DM, Dehoff RT. Lung morphometry: A new generation of tools and experiments for organ, tissue, cell, molecular biology. Am J Physiol 265: L521‐L548, 1993.
 35. Boll DT, Lewin JS, Young P, Siwik ES, Gilkeson RC. Perfusion abnormalities in congenital and neoplastic pulmonary disease: Comparison of MR perfusion and multislice CT imaging. Eur Radiol 15: 1978‐1978, 2005.
 36. Bouquet C, Lamande N, Brand M, Gasc JM, Jullienne B, Faure G, Griscelli F, Opolon P, Connault E, Perricaudet M, Corvol P. Suppression of angiogenesis, tumor growth, and metastasis by adenovirus‐mediated gene transfer of human angiotensinogen. Mol Ther 14: 175‐175, 2006.
 37. Boussat S, Eddahibi S, Coste A, Fataccioli V, Gouge M, Housset B, Adnot S, Maitre B. Expression and regulation of vascular endothelial growth factor in human pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 279: L371‐L378, 2000.
 38. Brody JS, Stemmler EJ, DuBois AB. Longitudinal distribution of vascular resistance in the pulmonary arteries, capillaries, and veins. J Clin Invest 47: 783‐783, 1968.
 39. Brusselmans K, Compernolle V, Tjwa M, Wiesener MS, Maxwell PH, Collen D, Carmeliet P. Heterozygous deficiency of hypoxia‐inducible factor‐2alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J Clin Invest 111: 1519‐1519, 2003.
 40. Burdick MD, Murray LA, Keane MP, Xue YY, Zisman DA, Belperio JA, Strieter RM. CXCL11 attenuates bleomycin‐induced pulmonary fibrosis via inhibition of vascular remodeling. Am J Respir Crit Care Med 171: 261‐261, 2005.
 41. Bureau W, Van Slyke P, Jones J, Han RN, Ward NL, Stewart DJ, Dumont DJ. Chronic systemic delivery of angiopoietin‐2 reveals a possible independent angiogenic effect. Am J Physiol Heart Circ Physiol 291: H948‐H956, 2006.
 42. Burnham EL, Taylor WR, Quyyumi AA, Rojas M, Brigham KL, Moss M. Increased circulating endothelial progenitor cells are associated with survival in acute lung injury. Am J Respir Crit Care Med 172: 854‐854, 2005.
 43. Cabebe E, Wakelee H. Role of anti‐angiogenesis agents in treating NSCLC: Focus on bevacizumab and VEGFR tyrosine kinase inhibitors. Current treatment options in oncology 8: 15‐15, 2007.
 44. Caduff JH, Fischer LC, Burri PH. Scanning electron microscope study of the developing microvasculature in the postnatal rat lung. Anat Rec 216: 154‐154, 1986.
 45. Cagle PT, Langston C, Goodman JC, Thurlbeck WM. Autoradiographic assessment of the sequence of cellular proliferation in postpneumonectomy lung growth. Am J Respir Cell Mol Biol 3: 153‐153, 1990.
 46. Cagle PT, Thurlbeck WM. Postpneumonectomy compensatory lung growth. Am Rev Respir Dis 138: 1314‐1314, 1988.
 47. Caldwell RW, Blatteis CM. Effect of chronic hypoxia on angiotensin‐induced pulmonary vasoconstriction and converting enzyme activity in the rat. Proc Soc Exp Biol Med 172: 346‐346, 1983.
 48. Campen MJ, Tagaito Y, Li J, Balbir A, Tankersley CG, Smith P, Schwartz A, O'Donnell CP. Phenotypic variation in cardiovascular responses to acute hypoxic and hypercapnic exposure in mice. Physiol Genomics 20: 15‐15, 2004.
 49. Cao R, Eriksson A, Kubo H, Alitalo K, Cao Y, Thyberg J. Comparative evaluation of FGF‐2‐, VEGF‐A‐, and VEGF‐C‐induced angiogenesis, lymphangiogenesis, vascular fenestrations, and permeability. Circ Res 94: 664‐664, 2004.
 50. Cao Y, Cao R, Hedlund EM. R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways. J Mol Med 86: 785‐785, 2008.
 51. Cao Y, O'Reilly MS, Marshall B, Flynn E, Ji RW, Folkman J. Expression of angiostatin cDNA in a murine fibrosarcoma suppresses primary tumor growth and produces long‐term dormancy of metastases. J Clin Invest 101: 1055‐1055, 1998.
 52. Capen RL, Hanson WL, Latham LP, Dawson CA, Wagner WW Jr. Distribution of pulmonary capillary transit times in recruited networks. J Appl Physiol 69: 473‐473, 1990.
 53. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med 6: 389‐389, 2000.
 54. Carmeliet P. Angiogenesis in health and disease. Nat Med 9: 653‐653, 2003.
 55. Carrillo de Santa Pau E, Arias FC, Caso Pelaez E, Munoz Molina GM, Sanchez Hernandez I, Muguruza Trueba I, Moreno Balsalobre R, Sacristan Lopez S, Gomez Pinillos A, del Val Toledo Lobo M. Prognostic significance of the expression of vascular endothelial growth factors A, B, C, and D and their receptors R1, R2, and R3 in patients with nonsmall cell lung cancer. Cancer 115: 1701‐1712, 2009.
 56. Cerny FC, Dempsey JA, Reddan WG. Pulmonary gas exchange in nonnative residents of high altitude. J Clin Invest 52: 2993‐2993, 1973.
 57. Charan NB, Albert RK, Lakshminarayan S, Kirk W, Butler J. Factors affecting bronchial blood flow through bronchopulmonary anastomoses in dogs. Am Rev Respir Dis 134: 85‐85, 1986.
 58. Charan NB, Carvalho P. Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction. J Appl Physiol 82: 284‐284, 1997.
 59. Charan NB, Lakshminarayan S, Albert RK, Kirk W, Butler J. Hypoxia and hypercarbia increase bronchial blood flow through bronchopulmonary anastomoses in anesthetized dogs. Am Rev Respir Dis 134: 89‐89, 1986.
 60. Charan NB, Turk GM, Dhand R. Gross and subgross anatomy of bronchial circulation in sheep. J Appl Physiol 57: 658‐658, 1984.
 61. Cheng SL, Wang HC, Yu CJ, Tsao PN, Carmeliet P, Cheng SJ, Yang PC. Prevention of elastase‐induced emphysema in placenta growth factor knock‐out mice. Respir Res 10: 115, 2009.
 62. Chesnutt AN, Matthay MA, Tibayan FA, Clark JG. Early detection of type III procollagen peptide in acute lung injury. Pathogenetic and prognostic significance. Am J Respir Crit Care Med 156: 840‐840, 1997.
 63. Chollet‐Martin S, Montravers P, Gibert C, Elbim C, Desmonts JM, Fagon JY, Gougerot‐Pocidalo MA. High levels of interleukin‐8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome. Infect Immun 61: 4553‐4553, 1993.
 64. Christou H, Yoshida A, Arthur V, Morita T, Kourembanas S. Increased vascular endothelial growth factor production in the lungs of rats with hypoxia‐induced pulmonary hypertension. Am J Respir Cell Mol Biol 18: 768‐768, 1998.
 65. Clark J, Alvarez DF, Alexeyev M, King JA, Huang L, Yoder MC, Stevens T. Regulatory role for nucleosome assembly protein‐1 in the proliferative and vasculogenic phenotype of pulmonary endothelium. Am J Physiol Lung Cell Mol Physiol 294: L431‐L439, 2008.
 66. Clark JG, Milberg JA, Steinberg KP, Hudson LD. Type III procollagen peptide in the adult respiratory distress syndrome. Association of increased peptide levels in bronchoalveolar lavage fluid with increased risk for death. Ann Intern Med 122: 17‐17, 1995.
 67. Clark RA. The commonality of cutaneous wound repair and lung injury. Chest 99: 57S‐60S, 1991.
 68. Clark RA. Basics of cutaneous wound repair. J Dermatol Surg Oncol 19: 693‐693, 1993.
 69. Clark‐Lewis I, Dewald B, Geiser T, Moser B, Baggiolini M. Platelet factor 4 binds to interleukin 8 receptors and activates neutrophils when its N terminus is modified with Glu‐Leu‐Arg. Proc Natl Acad Sci USA 90: 3574‐3574, 1993.
 70. Cockett F, Vass C. A comparison of the role of the bronchial arteries in bronchiectasis and in experimental ligation of the pulmonary artery. Thorax 2: 268, 1951.
 71. Cool CD, Groshong SD, Rai PR, Henson PM, Stewart JS, Brown KK. Fibroblast foci are not discrete sites of lung injury or repair: The fibroblast reticulum. Am J Respir Crit Care Med 174: 654‐654, 2006.
 72. Cosgrove GP, Brown KK, Schiemann WP, Serls AE, Parr JE, Geraci MW, Schwarz MI, Cool CD, Worthen GS. Pigment epithelium‐derived factor in idiopathic pulmonary fibrosis: A role in aberrant angiogenesis. Am J Respir Crit Care Med 170: 242‐242, 2004.
 73. Costello CM, Cahill E, Martin F, Gaine S, McLoughlin P. Role of gremlin in the lung: Development and disease. Am J Respir Cell Mol Biol 42: 517‐517, 2010.
 74. Costello CM, Howell K, Cahill E, McBryan J, Konigshoff M, Eickelberg O, Gaine S, Martin F, McLoughlin P. Lung‐selective gene responses to alveolar hypoxia: Potential role for the bone morphogenetic antagonist gremlin in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 295: L272‐L284, 2008.
 75. Cross MJ, Claesson‐Welsh L. FGF and VEGF function in angiogenesis: Signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci 22: 201‐201, 2001.
 76. Cudkowicz L, Armstrong JB. The blood supply of malignant pulmonary neoplasms. Thorax 8: 153‐153, 1953.
 77. Cui A, Anhenn O, Theegarten D, Ohshimo S, Bonella F, Sixt SU, Peters J, Sarria R, Guzman J, Costabel U. Angiogenic and angiostatic chemokines in idiopathic pulmonary fibrosis and granulomatous lung disease. Respiration 80: 372‐372, 2009.
 78. Cunningham EL, Brody JS, Jain BP. Lung growth induced by hypoxia. J Appl Physiol 37: 362‐362, 1974.
 79. D'Arcangelo D, Gaetano C, Capogrossi MC. Acidification prevents endothelial cell apoptosis by Axl activation. Circ Res 91: e4‐e12, 2002.
 80. David L, Mallet C, Keramidas M, Lamande N, Gasc JM, Dupuis‐Girod S, Plauchu H, Feige JJ, Bailly S. Bone morphogenetic protein‐9 is a circulating vascular quiescence factor. Circ Res 102: 914‐914, 2008.
 81. David L, Mallet C, Mazerbourg S, Feige JJ, Bailly S. Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor‐like kinase 1 (ALK1) in endothelial cells. Blood 109: 1953‐1953, 2007.
 82. Davidson JM. Wound repair. In: Gallin JI, Goldstein IM, Snyderman R, editor. Inflammation: Basic Principles and Clinical Correlates. New York: Raven Press Ltd, 1992, p. 809‐809.
 83. Dawson CA, Krenz GS, Karau KL, Haworth ST, Hanger CC, Linehan JH. Structure‐function relationships in the pulmonary arterial tree. J Appl Physiol 86: 569‐569, 1999.
 84. Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W, Bouck NP. Pigment epithelium‐derived factor: A potent inhibitor of angiogenesis. Science 285: 245‐245, 1999.
 85. de Jesus Perez VA, Alastalo TP, Wu JC, Axelrod JD, Cooke JP, Amieva M, Rabinovitch M. Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt‐beta‐catenin and Wnt‐RhoA‐Rac1 pathways. J Cell Biol 184: 83‐83, 2009.
 86. DeLisser HM, Newman PJ, Albelda SM. Molecular and functional aspects of PECAM‐1/CD31. Immunol Today 15: 490‐490, 1994.
 87. Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, Venetos G, Kalachikov S, Cayanis E, Fischer SG, Barst RJ, Hodge SE, Knowles JA. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor‐II gene. Am J Hum Genet 67: 737‐737, 2000.
 88. Derks CM, De Francquen P. Distribution of ventilation‐perfusion ratios in pneumonectomized dogs. Respiration 39: 61‐61, 1980.
 89. Detoraki A, Staiano RI, Granata F, Giannattasio G, Prevete N, de Paulis A, Ribatti D, Genovese A, Triggiani M, Marone G. Vascular endothelial growth factors synthesized by human lung mast cells exert angiogenic effects. J Allergy Clin Immunol 123: 1142‐1142, 1149 e1141‐e1145, 2009.
 90. Devesa SS, Blot WJ, Stone BJ, Miller BA, Tarone RE, Fraumeni JF Jr. Recent cancer trends in the United States [see comments]. J Natl Cancer Inst 87: 175‐175, 1995.
 91. Diab KJ, Adamowicz JJ, Kamocki K, Rush NI, Garrison J, Gu Y, Schweitzer KS, Skobeleva A, Rajashekhar G, Hubbard WC, Berdyshev EV, Petrache I. Stimulation of sphingosine 1‐phosphate signaling as an alveolar cell survival strategy in emphysema. Am J Respir Crit Care Med 181: 344‐344.
 92. Dineen SP, Lynn KD, Holloway SE, Miller AF, Sullivan JP, Shames DS, Beck AW, Barnett CC, Fleming JB, Brekken RA. Vascular endothelial growth factor receptor 2 mediates macrophage infiltration into orthotopic pancreatic tumors in mice. Cancer Res 68: 4340‐4340, 2008.
 93. Djonov V, Schmid M, Tschanz SA, Burri PH. Intussusceptive angiogenesis: Its role in embryonic vascular network formation. Circ Res 86: 286‐286, 2000.
 94. Djonov VG, Galli AB, Burri PH. Intussusceptive arborization contributes to vascular tree formation in the chick chorio‐allantoic membrane. Anat Embryol (Berl) 202: 347‐347, 2000.
 95. Djonov VG, Kurz H, Burri PH. Optimality in the developing vascular system: Branching remodeling by means of intussusception as an efficient adaptation mechanism. Dev Dyn 224: 391‐391, 2002.
 96. Do e Z, Fukumoto Y, Takaki A, Tawara S, Ohashi J, Nakano M, Tada T, Saji K, Sugimura K, Fujita H, Hoshikawa Y, Nawata J, Kondo T, Shimokawa H. Evidence for Rho‐kinase activation in patients with pulmonary arterial hypertension. Circ J 73: 1731‐1731, 2009.
 97. Donnelly SC, Strieter RM, Kunkel SL, Walz A, Robertson CR, Carter DC, Grant IS, Pollock AJ, Haslett C. Interleukin‐8 and development of adult respiratory distress syndrome in at‐risk patient groups. Lancet 341: 643‐643, 1993.
 98. Donnelly SC, Strieter RM, Reid PT, Kunkel SL, Burdick MD, Armstrong I, Mackenzie A, Haslett C. The association between mortality rates and decreased concentrations of interleukin‐10 and interleukin‐1 receptor antagonist in the lung fluids of patients with the adult respiratory distress syndrome. Ann Intern Med 125: 191‐191, 1996.
 99. Douglas IS, Diaz del Valle F, Winn RA, Voelkel NF. Beta‐catenin in the fibroproliferative response to acute lung injury. Am J Respir Cell Mol Biol 34: 274‐274, 2006.
 100. Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL, Yuan JX, Deutsch R, Jamieson SW, Thistlethwaite PA. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 348: 500‐500, 2003.
 101. Dutly AE, Andrade CF, Verkaik R, Kugathasan L, Trogadis J, Liu M, Waddell TK, Stewart DJ, Keshavjee S. A novel model for post‐transplant obliterative airway disease reveals angiogenesis from the pulmonary circulation. Am J Transplant 5: 248‐248, 2005.
 102. Dutly AE, Kugathasan L, Trogadis JE, Keshavjee SH, Stewart DJ, Courtman DW. Fluorescent microangiography (FMA): An improved tool to visualize the pulmonary microvasculature. Lab Invest 86: 409‐409, 2006.
 103. Ebina M, Shimizukawa M, Shibata N, Kimura Y, Suzuki T, Endo M, Sasano H, Kondo T, Nukiwa T. Heterogeneous increase in CD34‐positive alveolar capillaries in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 169: 1203‐1203, 2004.
 104. Emery CJ, Bee D, Barer GR. Mechanical properties and reactivity of vessels in isolated perfused lungs of chronically hypoxic rats. Clin Sci (Lond) 61: 569‐569, 1981.
 105. Endrys J, Hayat N, Cherian G. Comparison of bronchopulmonary collaterals and collateral blood flow in patients with chronic thromboembolic and primary pulmonary hypertension. Heart 78: 171‐171, 1997.
 106. Everett AD, Narron JV, Stoops T, Nakamura H, Tucker A. Hepatoma‐derived growth factor is a pulmonary endothelial cell‐expressed angiogenic factor. Am J Physiol Lung Cell Mol Physiol 286: L1194‐L1201, 2004.
 107. Ezaki T, Baluk P, Thurston G, La Barbara A, Woo C, McDonald DM. Time course of endothelial cell proliferation and microvascular remodeling in chronic inflammation. Am J Pathol 158: 2043‐2043, 2001.
 108. Fadel E, Wijtenburg E, Michel R, Mazoit JX, Bernatchez R, Decante B, Sage E, Mazmanian M, Herve P. Regression of the systemic vasculature to the lung after removal of pulmonary artery obstruction. Am J Respir Crit Care Med 173: 345‐345, 2006.
 109. Fagan KA, Oka M, Bauer NR, Gebb SA, Ivy DD, Morris KG, McMurtry IF. Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho‐kinase. Am J Physiol Lung Cell Mol Physiol 287: L656‐L664, 2004.
 110. Farkas L, Farkas D, Ask K, Moller A, Gauldie J, Margetts P, Inman M, Kolb M. VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J Clin Invest 119: 1298‐1298, 2009.
 111. Favre CJ, Mancuso M, Maas K, McLean JW, Baluk P, McDonald DM. Expression of genes involved in vascular development and angiogenesis in endothelial cells of adult lung. Am J Physiol Heart Circ Physiol 285: H1917‐H1938, 2003.
 112. Fehrenbach H, Kasper M, Haase M, Schuh D, Muller M. Differential immunolocalization of VEGF in rat and human adult lung, in experimental rat lung fibrosis: Light, fluorescence, and electron microscopy. Anat Rec 254: 61‐61, 1999.
 113. Fehrenbach H, Voswinckel R, Michl V, Mehling T, Fehrenbach A, Seeger W, Nyengaard JR. Neoalveolarisation contributes to compensatory lung growth following pneumonectomy in mice. Eur Respir J 31: 515‐515, 2008.
 114. Fernandez LG, Le Cras TD, Ruiz M, Glover DK, Kron IL, Laubach VE. Differential vascular growth in postpneumonectomy compensatory lung growth. J Thorac Cardiovasc Surg 133: 309‐309, 2007.
 115. Ferrara N. Vascular endothelial growth factor. Arterioscler Thromb Vasc Biol 29: 789‐789, 2009.
 116. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 9: 669‐669, 2003.
 117. Ferrer FA, Miller LJ, Andrawis RI, Kurtzman SH, Albertsen PC, Laudone VP, Kreutzer DL. Angiogenesis and prostate cancer: In vivo and in vitro expression of angiogenesis factors by prostate cancer cells. Urology 51: 161‐161, 1998.
 118. Fidler IJ. Critical factors in the biology of human cancer metastasis: Twenty‐Eighth G.H. A. Clowes Memorial Award Lecture. Cancer Research 50: 6130‐6130, 1990.
 119. Fidler IJ. Critical determinants of cancer metastasis: Rationale for therapy. Cancer Chemother Pharmacol 43: S3‐S10, 1999.
 120. Fields MJ, Bishai JM, Mitzner W, Wagner EM. Effects of pulmonary ischemia on lung morphology. Am J Physiol Lung Cell Mol Physiol 293: L254‐L258, 2007.
 121. Finlay M, Barer GR, Suggett AJ. Quantitative changes in the rat pulmonary vasculature in chronic hypoxia—relation to haemodynamic changes. Q J Exp Physiol 71: 151‐151, 1986.
 122. Flaherty KR, Travis WD, Colby TV, Toews GB, Kazerooni EA, Gross BH, Jain A, Strawderman RL, Flint A, Lynch JP, Martinez FJ. Histopathologic variability in usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 164: 1722‐1722, 2001.
 123. Foster DJ, Moe OW, Hsia CC. Upregulation of erythropoietin receptor during postnatal and postpneumonectomy lung growth. Am J Physiol Lung Cell Mol Physiol 287: L1107‐L1115, 2004.
 124. Fox SH, Whalen GF, Sanders MM, Burleson JA, Jennings K, Kurtzman S, Kreutzer D. Angiogenesis in normal tissue adjacent to colon cancer. J Surg Oncol 69: 230‐230, 1998.
 125. Frank DB, Abtahi A, Yamaguchi DJ, Manning S, Shyr Y, Pozzi A, Baldwin HS, Johnson JE, de Caestecker MP. Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension. Circ Res 97: 496‐496, 2005.
 126. Friesel RE, Maciag T. Molecular mechanisms of angiogenesis: Fibroblast growth factor signal transduction. FASEB J 9: 919‐919, 1995.
 127. Fudala R, Krupa A, Matthay MA, Allen TC, Kurdowska AK. Anti‐IL‐8 autoantibody: IL‐8 immune complexes suppress spontaneous apoptosis of neutrophils. Am J Physiol Lung Cell Mol Physiol 293: L364‐L374, 2007.
 128. Fudala R, Krupa A, Stankowska D, Allen TC, Kurdowska AK. Anti‐interleukin‐8 autoantibody: Interleukin‐8 immune complexes in acute lung injury/acute respiratory distress syndrome. Clin Sci (Lond) 114: 403‐403, 2008.
 129. Fukumura D, Gohongi T, Kadambi A, Izumi Y, Ang J, Yun CO, Buerk DG, Huang PL, Jain RK. Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor‐induced angiogenesis and vascular permeability. Proc Natl Acad Sci U S A 98: 2604‐2604, 2001.
 130. Gale GE, Torre‐Bueno JR, Moon RE, Saltzman HA, Wagner PD. Ventilation‐perfusion inequality in normal humans during exercise at sea level and simulated altitude. J Appl Physiol 58: 978‐978, 1985.
 131. Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V. Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science 319: 195‐195, 2008.
 132. Garcia JG, Liu F, Verin AD, Birukova A, Dechert MA, Gerthoffer WT, Bamberg JR, English D. Sphingosine 1‐phosphate promotes endothelial cell barrier integrity by Edg‐dependent cytoskeletal rearrangement. J Clin Invest 108: 689‐689, 2001.
 133. Gazzerro E, Canalis E. Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord 7: 51‐51, 2006.
 134. Gerrits H, van Ingen Schenau DS, Bakker NE, van Disseldorp AJ, Strik A, Hermens LS, Koenen TB, Krajnc‐Franken MA, Gossen JA. Early postnatal lethality and cardiovascular defects in CXCR7‐deficient mice. Genesis 46: 235‐235, 2008.
 135. Giatromanolaki A, Koukourakis M, O'Byrne K, Fox S, Whitehouse R, Talbot DC, Harris AL, Gatter KC. Prognostic value of angiogenesis in operable non‐small cell lung cancer. J Pathol 179: 80‐80, 1996.
 136. Glazier JB, Hughes JM, Maloney JE, West JB. Measurements of capillary dimensions and blood volume in rapidly frozen lungs. J Appl Physiol 26: 65‐65, 1969.
 137. Goumans MJ, Lebrin F, Valdimarsdottir G. Controlling the angiogenic switch: A balance between two distinct TGF‐b receptor signaling pathways. Trends Cardiovasc Med 13: 301‐301, 2003.
 138. Grabherr S, Djonov V, Yen K, Thali MJ, Dirnhofer R. Postmortem angiography: Review of former and current methods. AJR Am J Roentgenol 188: 832‐832, 2007.
 139. Griffioen AW, Molema G. Angiogenesis: Potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol Rev 52: 237‐237, 2000.
 140. Grocott MP, Martin DS, Levett DZ, McMorrow R, Windsor J, Montgomery HE. Arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med 360: 140‐140, 2009.
 141. Grover R, Wagner W, McMurtry I, Reeves J. Pulmonary circulation. In: Fishman A, editor. The Respiratory System. Bethesda, MD: American Physiological Society, 1985, p. 103‐103.
 142. Gundersen HJ, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, and West MJ. The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. Apmis 96: 857‐857, 1988.
 143. Gundersen HJ, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, and West MJ. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. Apmis 96: 379‐379, 1988.
 144. Hakim TS, Michel RP, Chang HK. Partitioning of pulmonary vascular resistance in dogs by arterial and venous occlusion. J Appl Physiol 52: 710‐710, 1982.
 145. Hamada N, Kuwano K, Yamada M, Hagimoto N, Hiasa K, Egashira K, Nakashima N, Maeyama T, Yoshimi M, Nakanishi Y. Anti‐vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice. J Immunol 175: 1224‐1224, 2005.
 146. Hanson WL, Emhardt JD, Bartek JP, Latham LP, Checkley LL, Capen RL, Wagner WW Jr. Site of recruitment in the pulmonary microcirculation. J Appl Physiol 66: 2079‐2079, 1989.
 147. Harper SJ, Bates DO. VEGF‐A splicing: The key to anti‐angiogenic therapeutics? Nat Rev Cancer 8: 880‐880, 2008.
 148. Harrison RE, Berger R, Haworth SG, Tulloh R, Mache CJ, Morrell NW, Aldred MA, Trembath RC. Transforming growth factor‐beta receptor mutations and pulmonary arterial hypertension in childhood. Circulation 111: 435‐435, 2005.
 149. Harrison RE, Flanagan JA, Sankelo M, Abdalla SA, Rowell J, Machado RD, Elliott CG, Robbins IM, Olschewski H, McLaughlin V, Gruenig E, Kermeen F, Halme M, Raisanen‐Sokolowski A, Laitinen T, Morrell NW, Trembath RC. Molecular and functional analysis identifies ALK‐1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J Med Genet 40: 865‐865, 2003.
 150. Hasegawa I, Kobayashi K, Kohda E, Hiramatsu K. Bronchopulmonary arterial anastomosis at the precapillary level in human lung. Visualization using CT angiography compared with microangiography of autopsied lung. Acta Radiol 40: 578‐578, 1999.
 151. Hasleton PS. Adult respiratory distress syndrome. In: Hasleton PS, editor. Spencer's pathology of the lung, 5th edition. New York: McGraw‐Hill, 1996, p. 375‐375.
 152. Hattermann K, Held‐Feindt J, Lucius R, Muerkoster SS, Penfold MET, Schall TJ, Mentlein R. The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects. 70: 3299‐3299, 2010.
 153. Haworth SG, Rees PG, Taylor JF, Macartney FJ, de Leval M, Stark J. Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Effect of systemic pulmonary anastomosis. Br Heart J 45: 133‐133, 1981.
 154. Heinke J, Wehofsits L, Zhou Q, Zoeller C, Baar KM, Helbing T, Laib A, Augustin H, Bode C, Patterson C, Moser M. BMPER is an endothelial cell regulator and controls bone morphogenetic protein‐4‐dependent angiogenesis. Circ Res 103: 804‐804, 2008.
 155. Henke C, Fiegel V, Peterson M, Wick M, Knighton D, McCarthy J, Bitterman P. Identification and partial characterization of angiogenesis bioactivity in the lower respiratory tract after acute lung injury. J Clin Invest 88: 1386‐1386, 1991.
 156. Hewett PW, Murray JC. Coexpression of flt‐1, flt‐4 and KDR in freshly isolated and cultured human endothelial cells. Biochem Biophys Res Commun 221: 697‐697, 1996.
 157. Hinder F, Matsumoto N, Booke M, Bradford DW, Traber LD, Herndon DN, Traber DL. Inhalation injury increases the anastomotic bronchial blood flow in the pouch model of the left ovine lung. Shock 8: 131‐131, 1997.
 158. Hislop A, Reid L. New findings in pulmonary arteries of rats with hypoxia‐induced pulmonary hypertension. Br J Exp Pathol 57: 542‐542, 1976.
 159. Hislop A, Reid L. Changes in the pulmonary arteries of the rat during recovery from hypoxia‐induced pulmonary hypertension. Br J Exp Pathol 58: 653‐653, 1977.
 160. Hislop AA. Airway and blood vessel interaction during lung development. J Anat 201: 325‐325, 2002.
 161. Hlushchuk R, Riesterer O, Baum O, Wood J, Gruber G, Pruschy M, Djonov V. Tumor recovery by angiogenic switch from sprouting to intussusceptive angiogenesis after treatment with PTK787/ZK222584 or ionizing radiation. Am J Pathol 173: 1173‐1173, 2008.
 162. Hodges MR, Forster HV, Papanek PE, Dwinell MR, Hogan GE. Ventilatory phenotypes among four strains of adult rats. J Appl Physiol 93: 974‐974, 2002.
 163. Hong KH, Lee YJ, Lee E, Park SO, Han C, Beppu H, Li E, Raizada MK, Bloch KD, Oh SP. Genetic ablation of the BMPR2 gene in pulmonary endothelium is sufficient to predispose to pulmonary arterial hypertension. Circulation 118: 722‐722, 2008.
 164. Hopkins N, Cadogan E, Giles S, McLoughlin P. Chronic airway infection leads to angiogenesis in the pulmonary circulation. J Appl Physiol 91: 919‐919, 2001.
 165. Hopkins N, McLoughlin P. The structural basis of pulmonary hypertension in chronic lung disease: Remodelling, rarefaction or angiogenesis? J Anat 201: 335‐335, 2002.
 166. Horn L, Sandler AB. Angiogenesis in the treatment of non‐small cell lung cancer. Proc Am Thorac Soc 6: 206‐206, 2009.
 167. Howell K, Costello CM, Sands M, Dooley I, McLoughlin P. L‐Arginine promotes angiogenesis in the chronically hypoxic lung: A novel mechanism ameliorating pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 296: L1042‐L1050, 2009.
 168. Howell K, Hopkins N, McLoughlin P. Combined confocal microscopy and stereology: A highly efficient and unbiased approach to quantitative structural measurement in tissues. Exp Physiol 87: 747‐747, 2002.
 169. Howell K, Ooi H, Preston R, McLoughlin P. Structural basis of hypoxic pulmonary hypertension: The modifying effect of chronic hypercapnia. Exp Physiol 89: 66‐66, 2004.
 170. Howell K, Preston RJ, McLoughlin P. Chronic hypoxia causes angiogenesis in addition to remodelling in the adult rat pulmonary circulation. J Physiol 547: 133‐133, 2003.
 171. Hsia CC. Lessons from a canine model of compensatory lung growth. Curr Top Dev Biol 64: 17‐17, 2004a.
 172. Hsia CC. Signals and mechanisms of compensatory lung growth. J Appl Physiol 97: 1992‐1992, 2004b.
 173. Hsia CC, Herazo LF, Fryder‐Doffey F, Weibel ER. Compensatory lung growth occurs in adult dogs after right pneumonectomy. J Clin Invest 94: 405‐405, 1994.
 174. Hsia CC, Herazo LF, Ramanathan M, Johnson RL Jr. Cardiopulmonary adaptations to pneumonectomy in dogs. IV. Membrane diffusing capacity and capillary blood volume. J Appl Physiol 77: 998‐998, 1994.
 175. Hsia CC, Hyde DM, Ochs M, Weibel ER. An official research policy statement of the American Thoracic Society/European Respiratory Society: Standards for quantitative assessment of lung structure. Am J Respir Crit Care Med 181: 394‐394, 2010.
 176. Hsia CC, Johnson RL, Jr, Wu EY, Estrera AS, Wagner H, Wagner PD. Reducing lung strain after pneumonectomy impairs oxygen diffusing capacity but not ventilation‐perfusion matching. J Appl Physiol 95: 1370‐1370, 2003.
 177. Hsia CC, Wu EY, Wagner E, Weibel ER. Preventing mediastinal shift after pneumonectomy impairs regenerative alveolar tissue growth. Am J Physiol Lung Cell Mol Physiol 281: L1279‐L1287, 2001.
 178. Hyde DM, Henderson TS, Giri SN, Tyler NK, Stovall MY. Effect of murine gamma interferon on the cellular responses to bleomycin in mice. Exp Lung Res 14: 687‐687, 1988.
 179. Hyvelin JM, Howell K, Nichol A, Costello CM, Preston RJ, McLoughlin P. Inhibition of Rho‐kinase attenuates hypoxia‐induced angiogenesis in the pulmonary circulation. Circ Res 97: 185‐185, 2005.
 180. Idell S, Maunder R, Fein AM, Switalska HI, Tuszynski GP, McLarty J, Niewiarowski S. Platelet‐specific alpha‐granule proteins and thrombospondin in bronchoalveolar lavage in the adult respiratory distress syndrome. Chest 96: 1125‐1125, 1989.
 181. Isenberg JS, Martin‐Manso G, Maxhimer JB, Roberts DD. Regulation of nitric oxide signalling by thrombospondin 1: Implications for anti‐angiogenic therapies. Nat Rev Cancer 9: 182‐182, 2009.
 182. Ishizawa K, Kubo H, Yamada M, Kobayashi S, Suzuki T, Mizuno S, Nakamura T, Sasaki H. Hepatocyte growth factor induces angiogenesis in injured lungs through mobilizing endothelial progenitor cells. Biochem Biophys Res Commun 324: 276‐276, 2004.
 183. Iwakiri S, Mino N, Takahashi T, Sonobe M, Nagai S, Okubo K, Wada H, Date H, Miyahara R. Higher expression of chemokine receptor CXCR7 is linked to early and metastatic recurrence in pathological stage I nonsmall cell lung cancer. Cancer 115: 2580‐2580, 2009.
 184. Izikki M, Guignabert C, Fadel E, Humbert M, Tu L, Zadigue P, Dartevelle P, Simonneau G, Adnot S, Maitre B, Raffestin B, Eddahibi S. Endothelial‐derived FGF2 contributes to the progression of pulmonary hypertension in humans and rodents. J Clin Invest 119: 512‐512, 2009.
 185. Jain RK. Molecular regulation of vessel maturation. Nat Med 9: 685‐685, 2003.
 186. Jancelewicz T, Grethel EJ, Chapin CJ, Clifton MS, Nobuhara KK. Vascular endothelial growth factor isoform and receptor expression during compensatory lung growth. J Surg Res 160: 107‐107, 2010.
 187. Jin E, Ghazizadeh M, Fujiwara M, Nagashima M, Shimizu H, Ohaki Y, Arai S, Gomibuchi M, Takemura T, Kawanami O. Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma. Pathol Int 51: 691‐691, 2001.
 188. Jonas AM, Carrington CB. Vascular patterns in primary and secondary pulmonary tumors in the dog. Am J Pathol 56: 79‐79, 1969.
 189. Jordana M, Schulman J, McSharry C, Irving LB, Newhouse MT, Jordana G, Gauldie J. Heterogeneous proliferative characteristics of human adult lung fibroblast lines and clonally derived fibroblasts from control and fibrotic tissue. Am Rev Respir Dis 137: 579‐579, 1988.
 190. Karau KL, Johnson RH, Molthen RC, Dhyani AH, Haworth ST, Hanger CC, Roerig DL, Dawson CA. Microfocal X‐ray CT imaging and pulmonary arterial distensibility in excised rat lungs. Am J Physiol Heart Circ Physiol 281: H1447‐H1457, 2001.
 191. Kasahara Y, Tuder RM, Taraseviciene‐Stewart L, Le Cras TD, Abman S, Hirth PK, Waltenberger J, Voelkel NF. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 106: 1311‐1311, 2000.
 192. Katayose D, Ohe M, Yamauchi K, Ogata M, Shirato K, Fujita H, Shibahara S, Takishima T. Increased expression of PDGF A‐ and B‐chain genes in rat lungs with hypoxic pulmonary hypertension. Am J Physiol 264: L100‐L106, 1993.
 193. Kay JM, Suyama KL, Keane PM. Failure to show decrease in small pulmonary blood vessels in rats with experimental pulmonary hypertension. Thorax 37: 927‐927, 1982.
 194. Keane MP, Arenberg DA, Lynch JP, 3rd, Whyte RI, Iannettoni MD, Burdick MD, Wilke CA, Morris SB, Glass MC, DiGiovine B, Kunkel SL, Strieter RM. The CXC chemokines, IL‐8 and IP‐10, regulate angiogenic activity in idiopathic pulmonary fibrosis. J Immunol 159: 1437‐1437, 1997.
 195. Keane MP, Belperio JA, Arenberg DA, Burdick MD, Xu ZJ, Xue YY, Strieter RM. IFN‐gamma‐inducible protein‐10 attenuates bleomycin‐induced pulmonary fibrosis via inhibition of angiogenesis. J Immunol 163: 5686‐5686, 1999.
 196. Keane MP, Belperio JA, Burdick M, Lynch JP, 3rd, Fishbein MF, Strieter RM. ENA‐78 is an important angiogenic factor in idiopathic pulmonary fibrosis. Am J Resp Crit Care Med 164: 2239‐2239, 2001.
 197. Keane MP, Belperio JA, Moore TA, Moore BB, Arenberg DA, Smith RE, Burdick MD, Kunkel SL, Strieter RM. Neutralization of the CXC chemokine, macrophage inflammatory protein‐2, attenuates bleomycin‐induced pulmonary fibrosis. J Immunol 162: 5511‐5511, 1999.
 198. Keane MP, Belperio JA, Xue YY, Burdick MD, Strieter RM. Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer. J Immunol 172: 2853‐2853, 2004.
 199. Keane MP, Donnelly SC, Belperio JA, Goodman RB, Dy M, Burdick MD, Fishbein MC, Strieter RM. Imbalance in the expression of CXC chemokines correlates with bronchoalveolar lavage fluid angiogenic activity and procollagen levels in acute respiratory distress syndrome. J Immunol 169: 6515‐6515, 2002.
 200. Kiessling F, Greschus S, Lichy MP, Bock M, Fink C, Vosseler S, Moll J, Mueller MM, Fusenig NE, Traupe H, Semmler W. Volumetric computed tomography (VCT): A new technology for noninvasive, high‐resolution monitoring of tumor angiogenesis. Nat Med 10: 1133‐1133, 2004.
 201. Kijowski J, Baj‐Krzyworzeka M, Majka M, Reca R, Marquez LA, Christofidou‐Solomidou M, Janowska‐Wieczorek A, Ratajczak MZ. The SDF‐1‐CXCR4 axis stimulates VEGF secretion and activates integrins but does not affect proliferation and survival in lymphohematopoietic cells. Stem Cells 19: 453‐453, 2001.
 202. Kobayashi H, Pelster B, Piiper J, Scheid P. Diffusion and perfusion limitation in alveolar O2 exchange: Shape of the blood O2 equilibrium curve. Respir Physiol 83: 23‐23, 1991.
 203. Koch AE, Strieter RM. Chemokines in Disease. Austin, TX: R.G. Landes Co., Biomedical Publishers, 1996.
 204. Koch AE, Volin MV, Woods JM, Kunkel SL, Connors MA, Harlow LA, Woodruff DC, Burdick MD, Strieter RM. Regulation of angiogenesis by the C‐X‐C chemokines interleukin‐8 and epithelial neutrophil activating peptide 78 in the rheumatoid joint. Arthritis Rheum 44: 31‐31, 2001.
 205. Koli K, Myllarniemi M, Vuorinen K, Salmenkivi K, Ryynanen MJ, Kinnula VL, Keski‐Oja J. Bone morphogenetic protein‐4 inhibitor gremlin is overexpressed in idiopathic pulmonary fibrosis. Am J Pathol 169: 61‐61, 2006.
 206. Konig MF, Lucocq JM, Weibel ER. Demonstration of pulmonary vascular perfusion by electron and light microscopy. J Appl Physiol 75: 1877‐1877, 1993.
 207. Koyama S, Sato E, Haniuda M, Numanami H, Nagai S, Izumi T. Decreased level of vascular endothelial growth factor in bronchoalveolar lavage fluid of normal smokers and patients with pulmonary fibrosis. Am J Respir Crit Care Med 166: 382‐382, 2002.
 208. Krause DS, Fackler MJ, Civin CI, May WS. CD34: Structure, biology, and clinical utility. Blood 87: 1‐1, 1996.
 209. Kugathasan L, Dutly AE, Zhao YD, Deng Y, Robb MJ, Keshavjee S, Stewart DJ. Role of angiopoietin‐1 in experimental and human pulmonary arterial hypertension. Chest 128: 633S‐642S, 2005.
 210. Kugathasan L, Ray JB, Deng Y, Rezaei E, Dumont DJ, Stewart DJ. The angiopietin‐1‐Tie2 pathway prevents rather than promotes pulmonary arterial hypertension in transgenic mice. J Exp Med 206: 2221‐2221, 2009.
 211. Kukk E, Lymboussaki A, Taira S, Kaipainen A, Jeltsch M, Joukov V, Alitalo K. VEGF‐C receptor binding and pattern of expression with VEGFR‐3 suggests a role in lymphatic vascular development. Development 122: 3829‐3829, 1996.
 212. Kurz H, Burri PH, Djonov VG. Angiogenesis and vascular remodeling by intussusception: From form to function. News Physiol Sci 18: 65‐65, 2003.
 213. Ladha F, Bonnet S, Eaton F, Hashimoto K, Korbutt G, Thebaud B. Sildenafil improves alveolar growth and pulmonary hypertension in hyperoxia‐induced lung injury. Am J Respir Crit Care Med 172: 750‐750, 2005.
 214. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, Loyd JE, Nichols WC, Trembath RC. Heterozygous germline mutations in BMPR2, encoding a TGF‐beta receptor, cause familial primary pulmonary hypertension. Nat Genet 26: 81‐81, 2000.
 215. Langer C, Soria JC. The role of anti‐epidermal growth factor receptor and anti‐vascular endothelial growth factor therapies in the treatment of non‐small‐cell lung cancer. Clinical lung cancer 11: 82‐82, 2010.
 216. Lawler J, Sunday M, Thibert V, Duquette M, George EL, Rayburn H, Hynes RO. Thrombospondin‐1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest 101: 982‐982, 1998.
 217. Le Cras TD, Fernandez LG, Pastura PA, Laubach VE. Vascular growth and remodeling in compensatory lung growth following right lobectomy. J Appl Physiol 98: 1140‐1140, 2005.
 218. LeCouter J, Kowalski J, Foster J, Hass P, Zhang Z, Dillard‐Telm L, Frantz G, Rangell L, DeGuzman L, Keller GA, Peale F, Gurney A, Hillan KJ, Ferrara N. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 412: 877‐877, 2001.
 219. Lee J, Gray A, Yuan J, Luoh SM, Avraham H, Wood WI. Vascular endothelial growth factor‐related protein: A ligand and specific activator of the tyrosine kinase receptor Flt4. Proc Natl Acad Sci U S A 93: 1988‐1988, 1996.
 220. Leonard MO, Howell K, Madden SF, Costello CM, Higgins DG, Taylor CT, McLoughlin P. Hypoxia selectively activates the CREB family of transcription factors in the in vivo lung. Am J Respir Crit Care Med 178: 977‐977, 2008.
 221. Levi M, Moons L, Bouche A, Shapiro SD, Collen D, Carmeliet P. Deficiency of urokinase‐type plasminogen activator‐mediated plasmin generation impairs vascular remodeling during hypoxia‐induced pulmonary hypertension in mice. Circulation 103: 2014‐2014, 2001.
 222. Levoye A, Balabanian K, Baleux F, Bachelerie F, Lagane B. CXCR7 heterodimerizes with CXCR4 and regulates CXCL12‐mediated G protein signaling. Blood 113: 6085‐6085, 2009.
 223. Li Y, Wang MN, Li H, King KD, Bassi R, Sun H, Santiago A, Hooper AT, Bohlen P, Hicklin DJ. Active immunization against the vascular endothelial growth factor receptor flk1 inhibits tumor angiogenesis and metastasis. J Exp Med 195: 1575‐1575, 2002.
 224. Liebow AA, Hales MR, Lindskog GE. Enlargement of the bronchial arteries, and their anastomoses with the pulmonary arteries in bronchiectasis. Am J Pathol 25: 211‐211, 1949.
 225. Linehan JH, Bronikowski TA, Rickaby DA, Dawson CA. Hydrolysis of a synthetic angiotensin‐converting enzyme substrate in dog lungs. Am J Physiol 257: H2006‐H2016, 1989.
 226. Liu F, Verin AD, Wang P, Day R, Wersto RP, Chrest FJ, English DK, Garcia JG. Differential regulation of sphingosine‐1‐phosphate‐ and VEGF‐induced endothelial cell chemotaxis. Involvement of G(ialpha2)‐linked Rho kinase activity. Am J Respir Cell Mol Biol 24: 711‐711, 2001.
 227. Loetscher M, Gerber B, Loetscher P, Jones SA, Piali L, Clark‐Lewis I, Baggiolini M, Moser B. Chemokine receptor specific for IP10 and mig: Structure, function, and expression in activated T‐lymphocytes. J Exp Med 184: 963‐963, 1996.
 228. Loges S, Roncal C, Carmeliet P. Development of targeted angiogenic medicine. J Thromb Haemost 7: 21‐21, 2009.
 229. Long L, Crosby A, Yang X, Southwood M, Upton PD, Kim DK, Morrell NW. Altered bone morphogenetic protein and transforming growth factor‐beta signaling in rat models of pulmonary hypertension: Potential for activin receptor‐like kinase‐5 inhibition in prevention and progression of disease. Circulation 119: 566‐566, 2009.
 230. Long L, MacLean MR, Jeffery TK, Morecroft I, Yang X, Rudarakanchana N, Southwood M, James V, Trembath RC, Morrell NW. Serotonin increases susceptibility to pulmonary hypertension in BMPR2‐deficient mice. Circ Res 98: 818‐818, 2006.
 231. Louzier V, Raffestin B, Leroux A, Branellec D, Caillaud JM, Levame M, Eddahibi S, Adnot S. Role of VEGF‐B in the lung during development of chronic hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 284: L926‐L937, 2003.
 232. Luca R, Lijnen HR, Suffredini AF, Pepper MS, Steinberg KP, Martin TR, Pugin J. Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin. Thromb Haemost 87: 966‐966, 2002.
 233. Lukacs NW, Miller AL, Hogaboam CM. Chemokine receptors in asthma: Searching for the correct immune targets. J Immunol 171: 11‐11, 2003.
 234. Luster AD, Greenberg SM, Leder P. The IP‐10 chemokine binds to a specific cell surface heparan sulfate shared with platelet factor 4 and inhibits endothelial cell proliferation. J Exp Med 182: 219‐219, 1995.
 235. Lynch JP, Standiford TJ, Kunkel SL, Rolfe MW, Strieter RM. Neutrophilic alveolitis in idiopathic pulmonary fibrosis: The role of interleukin‐8. Am Rev Respir Disease 145: 1433‐1433, 1992.
 236. Mae M, O'Connor TP, Crystal RG. Gene transfer of the vascular endothelial growth factor receptor flt‐1 suppresses pulmonary metastasis associated with lung growth. Am J Respir Cell Mol Biol 33: 629‐629, 2005.
 237. Magno M. Comparative anatomy of the tracheobronchial circulation. Eur Respir J Suppl 12: 557S‐562S; discussion 562S‐563S, 1990.
 238. Mahmoud M, Borthwick GM, Hislop AA, Arthur HM. Endoglin and activin receptor‐like‐kinase 1 are co‐expressed in the distal vessels of the lung: Implications for two familial vascular dysplasias, HHT and PAH. Lab Invest 89: 15‐15, 2009.
 239. Marcellini M, De Luca N, Riccioni T, Ciucci A, Orecchia A, Lacal PM, Ruffini F, Pesce M, Cianfarani F, Zambruno G, Orlandi A, Failla CM. Increased melanoma growth and metastasis spreading in mice overexpressing placenta growth factor. Am J Pathol 169: 643‐643, 2006.
 240. Marlier A, Schmidt‐Ott KM, Gallagher AR, Barasch J, Karihaloo A. VEGF as an epithelial cell morphogen modulates branching morphogenesis of embryonic kidney by directly acting on the ureteric bud. Mech Dev 126: 91‐98, 2009.
 241. Marti HH, Risau W. Systemic hypoxia changes the organ‐specific distribution of vascular endothelial growth factor and its receptors. Proc Natl Acad Sci U S A 95: 15809‐15809, 1998.
 242. Martin JS, Dickson MC, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ. Analysis of homozygous TGF beta 1 null mouse embryos demonstrates defects in yolk sac vasculogenesis and hematopoiesis. Ann N Y Acad Sci 752: 300‐300, 1995.
 243. Marwick JA, Stevenson CS, Giddings J, MacNee W, Butler K, Rahman I, Kirkham PA. Cigarette smoke disrupts VEGF165‐VEGFR‐2 receptor signaling complex in rat lungs and patients with COPD: Morphological impact of VEGFR‐2 inhibition. Am J Physiol Lung Cell Mol Physiol 290: L897‐L908, 2006.
 244. McClintock JY, Wagner EM. Role of IL‐6 in systemic angiogenesis of the lung. J Appl Physiol 99: 861‐861, 2005.
 245. McDonald JA. Idiopathic pulmonary fibrosis: A paradigm for lung injury and repair. Chest 99: 87S‐93S, 1991.
 246. McLoughlin P, McMurtry I. Counterpoint: Chronic hypoxia‐induced pulmonary hypertension does not lead to loss of pulmonary vasculature. J Appl Physiol 103: 1451‐1451; discussion 1453‐1453, 2007.
 247. Medford AR, Douglas SK, Godinho SI, Uppington KM, Armstrong L, Gillespie KM, van Zyl B, Tetley TD, Ibrahim NB, Millar AB. Vascular Endothelial Growth Factor (VEGF) isoform expression and activity in human and murine lung injury. Respir Res 10: 27, 2009.
 248. Medford AR, Ibrahim NB, Millar AB. Vascular endothelial growth factor receptor and coreceptor expression in human acute respiratory distress syndrome. J Crit Care 24: 236‐236, 2009.
 249. Medoff BD, Sauty A, Tager AM, Maclean JA, Smith RN, Mathew A, Dufour JH, Luster AD. IFN‐gamma‐inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma. J Immunol 168: 5278‐5278, 2002.
 250. Merker MP, Dawson CA, Bongard RD, Roerig DL, Haworth ST, Linehan JH. Angiotensin‐converting enzyme preferentially hydrolyzes trans isomer of proline‐containing substrate. J Appl Physiol 75: 1519‐1519, 1993.
 251. Merklinger SL, Wagner RA, Spiekerkoetter E, Hinek A, Knutsen RH, Kabir MG, Desai K, Hacker S, Wang L, Cann GM, Ambartsumian NS, Lukanidin E, Bernstein D, Husain M, Mecham RP, Starcher B, Yanagisawa H, Rabinovitch M. Increased fibulin‐5 and elastin in S100A4/Mts1 mice with pulmonary hypertension. Circ Res 97: 596‐596, 2005.
 252. Meyrick B, Reid L. Hypoxia and incorporation of 3 H‐thymidine by cells of the rat pulmonary arteries and alveolar wall. Am J Pathol 96: 51‐51, 1979.
 253. Miao Z, Luker KE, Summers BC, Berahovich R, Bhojani MS, Rehemtulla A, Kleer CG, Essner JJ, Nasevicius A, Luker GD, Howard MC, Schall TJ. CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor‐associated vasculature. Proc Natl Acad Sci U S A 104: 15735‐15735, 2007.
 254. Milne EN. Pulmonary metastases: Vascular supply and diagnosis. Int J Radiat Oncol Biol Phys 1: 739‐739, 1976.
 255. Milne EN, Zerhouni EA. Blood supply of pulmonary metastases. J Thorac Imaging 2: 15‐15, 1987.
 256. Mirshahi F, Pourtau J, Li H, Muraine M, Trochon V, Legrand E, Vannier J, Soria J, Vasse M, Soria C. SDF‐1 activity on microvascular endothelial cells: Consequences on angiogenesis in in vitro and in vivo models. Thromb Res 99: 587‐587, 2000.
 257. Mitzner W, Lee W, Georgakopoulos D, Wagner E. Angiogenesis in the mouse lung. Am J Pathol 157: 93‐93, 2000.
 258. Miyazono K, Kamiya Y, Morikawa M. Bone morphogenetic protein receptors and signal transduction. J Biochem 147: 35‐35, 2010.
 259. Modell HI, Beck K, Butler J. Functional aspects of canine bronchial‐pulmonary vascular communications. J Appl Physiol 50: 1045‐1045, 1981.
 260. Molthen RC, Karau KL, Dawson CA. Quantitative models of the rat pulmonary arterial tree morphometry applied to hypoxia‐induced arterial remodeling. J Appl Physiol 97: 2372‐2372; discussion 2354, 2004.
 261. Mooi W, Wagenvoort CA. Decreased numbers of pulmonary blood vessels: Reality or artifact? J Pathol 141: 441‐441, 1983.
 262. Morrell NW, Atochina EN, Morris KG, Danilov SM, Stenmark KR. Angiotensin converting enzyme expression is increased in small pulmonary arteries of rats with hypoxia‐induced pulmonary hypertension. J Clin Invest 96: 1823‐1823, 1995.
 263. Morrisey EE, Hogan BL. Preparing for the first breath: Genetic and cellular mechanisms in lung development. Dev Cell 18: 8‐8, 2010.
 264. Moser M, Binder O, Wu Y, Aitsebaomo J, Ren R, Bode C, Bautch VL, Conlon FL, Patterson C. BMPER, a novel endothelial cell precursor‐derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation. Mol Cell Biol 23: 5664‐5664, 2003.
 265. Mura M, Binnie M, Han B, Li C, Andrade CF, Shiozaki A, Zhang Y, Ferrara N, Hwang D, Waddell TK, Keshavjee S, Liu M. Functions of type II pneumocyte‐derived vascular endothelial growth factor in alveolar structure, acute inflammation, and vascular permeability. Am J Pathol 176: 1725‐1725, 2010.
 266. Murdoch C, Monk PN, Finn A. Cxc Chemokine Receptor Expression On Human Endothelial Cells. Cytokine 11: 704‐704, 1999.
 267. Murohara T, Asahara T, Silver M, Bauters C, Masuda H, Kalka C, Kearney M, Chen D, Symes JF, Fishman MC, Huang PL, Isner JM. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest 101: 2567‐2567, 1998.
 268. Myllarniemi M, Lindholm P, Ryynanen MJ, Kliment CR, Salmenkivi K, Keski‐Oja J, Kinnula VL, Oury TD, Koli K. Gremlin‐mediated decrease in bone morphogenetic protein signaling promotes pulmonary fibrosis. Am J Respir Crit Care Med 177: 321‐321, 2008.
 269. Nathan SD, Noble PW, Tuder RM. Idiopathic pulmonary fibrosis and pulmonary hypertension: Connecting the dots. Am J Respir Crit Care Med 175: 875‐875, 2007.
 270. Naumann U, Cameroni E, Pruenster M, Mahabaleshwar H, Raz E, Zerwes H‐GN, Rot A, Thelen M. CXCR7 Functions as a Scavenger for CXCL12 and CXCL11. PLoS ONE 5: e9175, 2010.
 271. Nelin LD, Roerig DL, Rickaby DA, Linehan JH, Dawson CA. Influence of flow on pulmonary vascular surface area inferred from blue dextran efflux data. J Appl Physiol 72: 874‐874, 1992.
 272. Niethammer AG, Xiang R, Becker JC, Wodrich H, Pertl U, Karsten G, Eliceiri BP, Reisfeld RA. A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med 8: 1369‐1369, 2002.
 273. Numasaki M, Watanabe M, Suzuki T, Takahashi H, Nakamura A, McAllister F, Hishinuma T, Goto J, Lotze MT, Kolls JK, Sasaki H. IL‐17 enhances the net angiogenic activity and in vivo growth of human non‐small cell lung cancer in SCID mice through promoting CXCR‐2‐dependent angiogenesis. J Immunol 175: 6177‐6177, 2005.
 274. O'Byrne KJ, Koukourakis MI, Giatromanolaki A, Cox G, Turley H, Steward WP, Gatter K, Harris AL. Vascular endothelial growth factor, platelet‐derived endothelial cell growth factor and angiogenesis in non‐small‐cell lung cancer. Br J Cancer 82: 1427‐1427, 2000.
 275. Oka M, Homma N, Taraseviciene‐Stewart L, Morris KG, Kraskauskas D, Burns N, Voelkel NF, McMurtry IF. Rho kinase‐mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats. Circ Res 100: 923‐923, 2007.
 276. Ono M, Sawa Y, Matsumoto K, Nakamura T, Kaneda Y, Matsuda H. In vivo gene transfection with hepatocyte growth factor via the pulmonary artery induces angiogenesis in the rat lung. Circulation 106: I264‐I269, 2002.
 277. Paddenberg R, Faulhammer P, Goldenberg A, Kummer W. Hypoxia‐induced increase of endostatin in murine aorta and lung. Histochem Cell Biol 125: 497‐497, 2006.
 278. Pan Y, Krueger T, Tran N, Yan H, Ris HB, McKee TA. Evaluation of tumour vascularisation in two rat sarcoma models for studying isolated lung perfusion. Injection route determines the origin of tumour vessels. Eur Surg Res 37: 92‐92, 2005.
 279. Papaioannou AI, Kostikas K, Kollia P, Gourgoulianis KI. Clinical implications for vascular endothelial growth factor in the lung: Friend or foe? Respir Res 7: 128, 2006.
 280. Papapetropoulos A, Garcia‐Cardena G, Madri JA, Sessa WC. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 100: 3131‐3131, 1997.
 281. Parera MC, van Dooren M, van Kempen M, de Krijger R, Grosveld F, Tibboel D, Rottier R. Distal angiogenesis: A new concept for lung vascular morphogenesis. Am J Physiol Lung Cell Mol Physiol 288: L141‐L149, 2005.
 282. Parra ER, Silverio da Costa LR, Ab'Saber A, Ribeiro de Carvalho CR, Kairalla RA, Fernezlian SM, Teixeira LR, Capelozzi VL. Nonhomogeneous density of CD34 and VCAM‐1 alveolar capillaries in major types of idiopathic interstitial pneumonia. Lung 183: 363‐363, 2005.
 283. Partovian C, Adnot S, Eddahibi S, Teiger E, Levame M, Dreyfus P, Raffestin B, Frelin C. Heart and lung VEGF mRNA expression in rats with monocrotaline‐ or hypoxia‐induced pulmonary hypertension. Am J Physiol 275: H1948‐H1956, 1998.
 284. Partovian C, Adnot S, Raffestin B, Louzier V, Levame M, Mavier IM, Lemarchand P, Eddahibi S. Adenovirus‐mediated lung vascular endothelial growth factor overexpression protects against hypoxic pulmonary hypertension in rats. Am J Respir Cell Mol Biol 23: 762‐762, 2000.
 285. Pascaud MA, Griscelli F, Raoul W, Marcos E, Opolon P, Raffestin B, Perricaudet M, Adnot S, Eddahibi S. Lung overexpression of angiostatin aggravates pulmonary hypertension in chronically hypoxic mice. Am J Respir Cell Mol Biol 29: 449‐449, 2003.
 286. Patan S, Munn LL, Tanda S, Roberge S, Jain RK, Jones RC. Vascular morphogenesis and remodeling in a model of tissue repair: Blood vessel formation and growth in the ovarian pedicle after ovariectomy. Circ Res 89: 723‐723, 2001.
 287. Peao MND, Aguas AP, DeSa CM, Grande NR. Neoformation of blood vessels in association with rat lung fibrosis induced by bleomycin. Anat Rec 238: 57‐57, 1994.
 288. Perkins GD, Roberts J, McAuley DF, Armstrong L, Millar A, Gao F, Thickett DR. Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury. Thorax 60: 153‐153, 2005.
 289. Petrache I, Natarajan V, Zhen L, Medler TR, Richter AT, Cho C, Hubbard WC, Berdyshev EV, Tuder RM. Ceramide upregulation causes pulmonary cell apoptosis and emphysema‐like disease in mice. Nat Med 11: 491‐491, 2005.
 290. Pettersson A, Nagy JA, Brown LF, Sundberg C, Morgan E, Jungles S, Carter R, Krieger JE, Manseau EJ, Harvey VS, Eckelhoefer IA, Feng D, Dvorak AM, Mulligan RC, Dvorak HF. Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor. Lab Invest 80: 99‐99, 2000.
 291. Pfeifer M, Blumberg FC, Wolf K, Sandner P, Elsner D, Riegger GA, Kurtz A. Vascular remodeling and growth factor gene expression in the rat lung during hypoxia. Respir Physiol 111: 201‐201, 1998.
 292. Phillips RJ, Burdick MD, Lutz M, Belperio JA, Keane MP, Strieter RM. The stromal derived factor‐1/CXCL12‐CXC chemokine receptor 4 biological axis in non‐small cell lung cancer metastases. Am J Respir Crit Care Med 167: 1676‐1676, 2003.
 293. Piali L, Hammel P, Uherek C, Bachmann F, Gisler RH, Dunon D, Imhof BA. CD31/PECAM‐1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol 130: 451‐451, 1995.
 294. Piiper J, Scheid P. Model for capillary‐alveolar equilibration with special reference to O2 uptake in hypoxia. Respir Physiol 46: 193‐193, 1981.
 295. Piiper J, Scheid P. Comparison of diffusion and perfusion limitations in alveolar gas exchange. Respir Physiol 51: 287‐287, 1983.
 296. Polunovsky VA, Chen B, Henke C, Snover D, Wendt C, Ingbar DH, Bitterman PB. Role of mesenchymal cell death in lung remodeling after injury. J Clin Invest 92: 388‐388, 1993.
 297. Pugin J, Verghese G, Widmer MC, Matthay MA. The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome. Crit Care Med 27: 304‐304, 1999.
 298. Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli‐1 in normal human tissues. J Histochem Cytochem 54: 385‐385, 2006.
 299. Qiu B, Frait KA, Reich F, Komuniecki E, Chensue SW. Chemokine expression dynamics in mycobacterial (type‐1) and schistosomal (type‐2) antigen‐elicited pulmonary granuloma formation. Am J Pathol 158: 1503‐1503, 2001.
 300. Rabinovitch M, Gamble W, Nadas AS, Miettinen OS, Reid L. Rat pulmonary circulation after chronic hypoxia: Hemodynamic and structural features. Am J Physiol 236: H818‐H827, 1979.
 301. Rabinovitch M, Gamble WJ, Miettinen OS, Reid L. Age and sex influence on pulmonary hypertension of chronic hypoxia and on recovery. Am J Physiol 240: H62‐H72, 1981.
 302. Rabinovitch M, Konstam MA, Gamble WJ, Papanicolaou N, Aronovitz MJ, Treves S, Reid L. Changes in pulmonary blood flow affect vascular response to chronic hypoxia in rats. Circ Res 52: 432‐432, 1983.
 303. Rajagopal S, Kim J, Ahn S, Craig S, Lam CM, Gerard NP, Gerard C, Lefkowitz RJ. Beta‐arrestin‐ but not G protein‐mediated signaling by the “decoy” receptor CXCR7. Proc Natl Acad Sci U S A 107: 628‐628, 2010.
 304. Ravid K, Beeler DL, Rabin MS, Ruley HE, Rosenberg RD. Selective targeting of gene products with the megakaryocyte platelet factor 4 promoter. Proc Natl Acad Sci U S A 88: 1521‐1521, 1991.
 305. Renzoni EA, Walsh DA, Salmon M, Wells AU, Sestini P, Nicholson AG, Veeraraghavan S, Bishop AE, Romanska HM, Pantelidis P, Black CM, Du Bois RM. Interstitial vascularity in fibrosing alveolitis. Am J Respir Crit Care Med 167: 438‐438, 2003.
 306. Reynolds A, Xia W, Holmes M, Hodge S, Danilov S, Curiel D, Morrell N, Reynolds P. Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 292: L1182‐L1192, 2007.
 307. Ribatti D, Vacca A, Nico B, Roncali L, Dammacco F. Postnatal vasculogenesis. Mech Dev 100: 157‐157, 2001.
 308. Richter A, Yeager ME, Zaiman A, Cool CD, Voelkel NF, Tuder RM. Impaired transforming growth factor‐beta signaling in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 170: 1340‐1340, 2004.
 309. Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol 11: 73‐73, 1995.
 310. Ristimaki A, Narko K, Enholm B, Joukov V, Alitalo K. Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor‐C. J Biol Chem 273: 8413‐8413, 1998.
 311. Roberts DD, Isenberg JS, Ridnour LA, Wink DA. Nitric oxide and its gatekeeper thrombospondin‐1 in tumor angiogenesis. Clin Cancer Res 13: 795‐795, 2007.
 312. Romagnani P, Annunziato F, Lasagni L, Lazzeri E, Beltrame C, Francalanci M, Uguccioni M, Galli G, Cosmi L, Maurenzig L, Baggiolini M, Maggi E, Romagnani S, Serio M. Cell cycle‐dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity. J Clin Invest 107: 53‐53, 2001.
 313. Rondelet B, Kerbaul F, Van Beneden R, Hubloue I, Huez S, Fesler P, Remmelink M, Brimioulle S, Salmon I, Naeije R. Prevention of pulmonary vascular remodeling and of decreased BMPR‐2 expression by losartan therapy in shunt‐induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 289: H2319‐H2324, 2005.
 314. Rosendahl A, Pardali E, Speletas M, Ten Dijke P, Heldin CH, Sideras P. Activation of bone morphogenetic protein/Smad signaling in bronchial epithelial cells during airway inflammation. Am J Respir Cell Mol Biol 27: 160‐160, 2002.
 315. Rosenzweig A. Endothelial progenitor cells. N Engl J Med 348: 581‐581, 2003.
 316. Ruiz de Almodovar C, Lambrechts D, Mazzone M, Carmeliet P. Role and therapeutic potential of VEGF in the nervous system. Physiol Rev 89: 607‐607, 2009.
 317. Saijo Y, Tanaka M, Miki M, Usui K, Suzuki T, Maemondo M, Hong X, Tazawa R, Kikuchi T, Matsushima K, Nukiwa T. Proinflammatory cytokine IL‐1 beta promotes tumor growth of Lewis lung carcinoma by induction of angiogenic factors: In vivo analysis of tumor‐stromal interaction. J Immunol 169: 469‐469, 2002.
 318. Sakamaki Y, Matsumoto K, Mizuno S, Miyoshi S, Matsuda H, Nakamura T. Hepatocyte growth factor stimulates proliferation of respiratory epithelial cells during postpneumonectomy compensatory lung growth in mice. Am J Respir Cell Mol Biol 26: 525‐525, 2002.
 319. Sakurai MK, Lee S, Arsenault DA, Nose V, Wilson JM, Heymach JV, Puder M. Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy. Am J Physiol Lung Cell Mol Physiol 292: L742‐L747, 2007.
 320. Salameh G, Karamsetty MR, Warburton RR, Klinger JR, Ou LC, Hill NS. Differences in acute hypoxic pulmonary vasoresponsiveness between rat strains: Role of endothelium. J Appl Physiol 87: 356‐356, 1999.
 321. Salcedo R, Wasserman K, Young HA, Grimm MC, Howard OM, Anver MR, Kleinman HK, Murphy WJ, Oppenheim JJ. Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal‐derived factor‐1alpha. Am J Pathol 154: 1125‐1125, 1999.
 322. Sanchez J, Moldobaeva A, McClintock J, Jenkins J, Wagner E. The role of CXCR2 in systemic neovascularization of the mouse lung. J Appl Physiol 103: 594‐594, 2007.
 323. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel‐carboplatin alone or with bevacizumab for non‐small‐cell lung cancer. N Engl J Med 355: 2542‐2542, 2006.
 324. Sandner P, Gess B, Wolf K, Kurtz A. Divergent regulation of vascular endothelial growth factor and of erythropoietin gene expression in vivo. Pflugers Arch 431: 905‐905, 1996.
 325. Sandner P, Wolf K, Bergmaier U, Gess B, Kurtz A. Hypoxia and cobalt stimulate vascular endothelial growth factor receptor gene expression in rats. Pflugers Arch 433: 803‐803, 1997.
 326. Sato K, Webb S, Tucker A, Rabinovitch M, O'Brien RF, McMurtry IF, Stelzner TJ. Factors influencing the idiopathic development of pulmonary hypertension in the fawn hooded rat. Am Rev Respir Dis 145: 793‐793, 1992.
 327. Satoh K, Kagaya Y, Nakano M, Ito Y, Ohta J, Tada H, Karibe A, Minegishi N, Suzuki N, Yamamoto M, Ono M, Watanabe J, Shirato K, Ishii N, Sugamura K, Shimokawa H. Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia‐induced pulmonary hypertension in mice. Circulation 113: 1442‐1442, 2006.
 328. Sauter BV, Martinet O, Zhang WJ, Mandeli J, Woo SL. Adenovirus‐mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases. Proc Natl Acad Sci U S A 97: 4802‐4802, 2000.
 329. Savai R, Langheinrich AC, Schermuly RT, Pullamsetti SS, Dumitrascu R, Traupe H, Rau WS, Seeger W, Grimminger F, Banat GA. Evaluation of angiogenesis using micro‐computed tomography in a xenograft mouse model of lung cancer. Neoplasia 11: 48‐48, 2009.
 330. Savai R, Wolf JC, Greschus S, Eul BG, Schermuly RT, Hanze J, Voswinckel R, Langheinrich AC, Grimminger F, Traupe H, Seeger W, Rose F. Analysis of tumor vessel supply in Lewis lung carcinoma in mice by fluorescent microsphere distribution and imaging with micro‐ and flat‐panel computed tomography. Am J Pathol 167: 937‐937, 2005.
 331. Schachtner SK, Wang Y, Scott Baldwin H. Qualitative and quantitative analysis of embryonic pulmonary vessel formation. Am J Respir Cell Mol Biol 22: 157‐157, 2000.
 332. Schaphorst KL, Chiang E, Jacobs KN, Zaiman A, Natarajan V, Wigley F, Garcia JG. Role of sphingosine‐1 phosphate in the enhancement of endothelial barrier integrity by platelet‐released products. Am J Physiol Lung Cell Mol Physiol 285: L258‐L267, 2003.
 333. Schatteman GC, Dunnwald M, Jiao C. Biology of bone marrow‐derived endothelial cell precursors. Am J Physiol Heart Circ Physiol 292: H1‐H18, 2007.
 334. Schraufnagel DE, Pearse DB, Mitzner WA, Wagner EM. Three‐dimensional structure of the bronchial microcirculation in sheep. Anat Rec 243: 357‐357, 1995.
 335. Schraufnagel DE, Sekosan M, McGee T, Thakkar MB. Human alveolar capillaries undergo angiogenesis in pulmonary veno‐ occlusive disease. Eur Respir J 9: 346‐346, 1996.
 336. Schwarz MA, Caldwell L, Cafasso D, Zheng H. Emerging pulmonary vasculature lacks fate specification. Am J Physiol Lung Cell Mol Physiol 296: L71‐L81, 2009.
 337. Schwenke DO, Pearson JT, Kangawa K, Umetani K, Shirai M. Changes in macrovessel pulmonary blood flow distribution following chronic hypoxia: Assessed using synchrotron radiation microangiography. J Appl Physiol 104: 88‐88, 2008.
 338. Selman M, Ruiz V, Cabrera S, Segura L, Ramirez R, Barrios R, Pardo A. TIMP‐1, ‐2, ‐3, and ‐4 in idiopathic pulmonary fibrosis. A prevailing nondegradative lung microenvironment? Am J Physiol Lung Cell Mol Physiol 279: L562‐L574, 2000.
 339. Sheppard D. Pulmonary fibrosis: A cellular overreaction or a failure of communication? J Clin Invest 107: 1501‐1501, 2001.
 340. Shi Y, Massague J. Mechanisms of TGF‐beta signaling from cell membrane to the nucleus. Cell 113: 685‐685, 2003.
 341. Sierro F, Biben C, Martinez‐Munoz L, Mellado M, Ransohoff RM, Li M, Woehl B, Leung H, Groom J, Batten M, Harvey RP, Martinez AC, Mackay CR, Mackay F. Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF‐1 receptor, CXCR7. Proc Natl Acad Sci U S A 104: 14759‐14759, 2007.
 342. Sime PJ, Gauldie J. Mechanisms of scarring. In: Evans TW, Haslett C, editors. ARDS‐Acute Respiratory Distress in Adults. London: Chapman & Hall Medical, 1996, p. 215‐215.
 343. Simler NR, Brenchley PE, Horrocks AW, Greaves SM, Hasleton PS, Egan JJ. Angiogenic cytokines in patients with idiopathic interstitial pneumonia. Thorax 59: 581‐581, 2004.
 344. Smith DR, Polverini PJ, Kunkel SL, Orringer MB, Whyte RI, Burdick MD, Wilke CA, Strieter RM. Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma. J Exp Med 179: 1409‐1409, 1994.
 345. Song N, Huang Y, Shi H, Yuan S, Ding Y, Song X, Fu Y, Luo Y. Overexpression of platelet‐derived growth factor‐BB increases tumor pericyte content via stromal‐derived factor‐1alpha/CXCR4 axis. Cancer Res 69: 6057‐6057, 2009.
 346. Song Y, Coleman L, Shi J, Beppu H, Sato K, Walsh K, Loscalzo J, Zhang YY. Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2‐mutant mice. Am J Physiol Heart Circ Physiol 295: H677‐H690, 2008.
 347. Song Y, Jones JE, Beppu H, Keaney JF Jr, Loscalzo J, Zhang YY. Increased susceptibility to pulmonary hypertension in heterozygous BMPR2‐mutant mice. Circulation 112: 553‐553, 2005.
 348. Southwood M, Jeffery TK, Yang X, Upton PD, Hall SM, Atkinson C, Haworth SG, Stewart S, Reynolds PN, Long L, Trembath RC, Morrell NW. Regulation of bone morphogenetic protein signalling in human pulmonary vascular development. J Pathol 214: 85‐85, 2008.
 349. Srinivasan S, Hanes MA, Dickens T, Porteous ME, Oh SP, Hale LP, Marchuk DA. A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2. Hum Mol Genet 12: 473‐473, 2003.
 350. Stenmark KR, Abman SH. Lung vascular development: Implications for the pathogenesis of bronchopulmonary dysplasia. Annu Rev Physiol 67: 623‐623, 2005.
 351. Stiebellehner L, Belknap JK, Ensley B, Tucker A, Orton EC, Reeves JT, Stenmark KR. Lung endothelial cell proliferation in normal and pulmonary hypertensive neonatal calves. Am J Physiol 275: L593‐L600, 1998.
 352. Strieter RM, Polverini PJ, Arenberg DA, Walz A, Opdenakker G, Van Damme J, Kunkel SL. Role of C‐X‐C chemokines as regulators of angiogenesis in lung cancer. J Leukoc Biol 57: 752‐752, 1995.
 353. Suratt BT, Cool CD, Serls AE, Chen L, Varella‐Garcia M, Shpall EJ, Brown KK, Worthen GS. Human pulmonary chimerism after hematopoietic stem cell transplantation. Am J Respir Crit Care Med 168: 318‐318, 2003.
 354. Tabata C, Tabata R, Kadokawa Y, Hisamori S, Takahashi M, Mishima M, Nakano T, Kubo H. Thalidomide prevents bleomycin‐induced pulmonary fibrosis in mice. J Immunol 179: 708‐708, 2007.
 355. Tabruyn SP, Griffioen AW. Molecular pathways of angiogenesis inhibition. Biochem Biophys Res Commun 355: 1‐1, 2007.
 356. Taft RA, Davisson M, Wiles MV. Know thy mouse. Trends Genet 22: 649‐649, 2006.
 357. Takahashi H, Goto N, Kojima Y, Tsuda Y, Morio Y, Muramatsu M, Fukuchi Y. Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 290: L450‐L458, 2006.
 358. Takahashi K, Kogaki S, Matsushita T, Nasuno S, Kurotobi S, Ozono K. Hypoxia induces alteration of bone morphogenetic protein receptor signaling in pulmonary artery endothelial cell. Pediatr Res 61: 392‐392, 2007.
 359. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T. Ischemia‐ and cytokine‐induced mobilization of bone marrow‐derived endothelial progenitor cells for neovascularization. Nat Med 5: 434‐434, 1999.
 360. Takeda K, Cowan A, Fong GH. Essential role for prolyl hydroxylase domain protein 2 in oxygen homeostasis of the adult vascular system. Circulation 116: 774‐774, 2007.
 361. Tang K, Rossiter HB, Wagner PD, Breen EC. Lung‐targeted VEGF inactivation leads to an emphysema phenotype in mice. J Appl Physiol 97: 1559‐1559; discussion 1549, 2004.
 362. Taraseviciene‐Stewart L, Kasahara Y, Alger L, Hirth P, Mc Mahon G, Waltenberger J, Voelkel NF, Tuder RM. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death‐dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 15: 427‐427, 2001.
 363. Taylor AP, Goldenberg DM. Role of placenta growth factor in malignancy and evidence that an antagonistic PlGF/Flt‐1 peptide inhibits the growth and metastasis of human breast cancer xenografts. Mol Cancer Ther 6: 524‐524, 2007.
 364. Teichert‐Kuliszewska K, Kutryk MJ, Kuliszewski MA, Karoubi G, Courtman DW, Zucco L, Granton J, Stewart DJ. Bone morphogenetic protein receptor‐2 signaling promotes pulmonary arterial endothelial cell survival: Implications for loss‐of‐function mutations in the pathogenesis of pulmonary hypertension. Circ Res 98: 209‐209, 2006.
 365. Tepper OM, Capla JM, Galiano RD, Ceradini DJ, Callaghan MJ, Kleinman ME, Gurtner GC. Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow‐derived cells. Blood 105: 1068‐1068, 2005.
 366. Thet LA, Law DJ. Changes in cell number and lung morphology during early postpneumonectomy lung growth. J Appl Physiol 56: 975‐975, 1984.
 367. Thickett DR, Armstrong L, Millar AB. A role for vascular endothelial growth factor in acute and resolving lung injury. Am J Respir Crit Care Med 166: 1332‐1332, 2002.
 368. Thurston G, Baluk P, McDonald DM. Determinants of endothelial cell phenotype in venules. Microcirculation 7: 67‐67, 2000.
 369. Thurston G, Murphy TJ, Baluk P, Lindsey JR, McDonald DM. Angiogenesis in mice with chronic airway inflammation: Strain‐dependent differences. Am J Pathol 153: 1099‐1099, 1998.
 370. Todd L, Mullen M, Olley PM, Rabinovitch M. Pulmonary toxicity of monocrotaline differs at critical periods of lung development. Pediatr Res 19: 731‐731, 1985.
 371. Tomashefski JF Jr, Davies P, Boggis C, Greene R, Zapol WM, Reid LM. The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol 112: 112‐112, 1983.
 372. Toporsian M, Jerkic M, Zhou YQ, Kabir MG, Yu LX, McIntyre BA, Davis A, Wang YJ, Stewart DJ, Belik J, Husain M, Henkelman M, Letarte M. Spontaneous adult‐onset pulmonary arterial hypertension attributable to increased endothelial oxidative stress in a murine model of hereditary hemorrhagic telangiectasia. Arterioscler Thromb Vasc Biol 30: 509‐509, 2010.
 373. Tsai AG, Friesenecker B, Mazzoni MC, Kerger H, Buerk DG, Johnson PC, Intaglietta M. Microvascular and tissue oxygen gradients in the rat mesentery. Proc Natl Acad Sci U S A 95: 6590‐6590, 1998.
 374. Tsao PN, Su YN, Li H, Huang PH, Chien CT, Lai YL, Lee CN, Chen CA, Cheng WF, Wei SC, Yu CJ, Hsieh FJ, Hsu SM. Overexpression of placenta growth factor contributes to the pathogenesis of pulmonary emphysema. Am J Respir Crit Care Med 169: 505‐505, 2004.
 375. Tsuchida K, Arai KY, Kuramoto Y, Yamakawa N, Hasegawa Y, Sugino H. Identification and characterization of a novel follistatin‐like protein as a binding protein for the TGF‐beta family. J Biol Chem 275: 40788‐40788, 2000.
 376. Tuder RM, Flook BE, Voelkel NF. Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. J Clin Invest 95: 1798‐1798, 1995.
 377. Turner‐Warwick M. Precapillary systemic‐pulmonary anastomoses. Thorax 18: 225‐225, 1963.
 378. Upton PD, Davies RJ, Trembath RC, Morrell NW. Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor‐like kinase‐1 in human pulmonary artery endothelial cells. J Biol Chem 284: 15794‐15794, 2009.
 379. Upton PD, Long L, Trembath RC, Morrell NW. Functional characterization of bone morphogenetic protein binding sites and Smad1/5 activation in human vascular cells. Mol Pharmacol 73: 539‐539, 2008.
 380. Vadivel A, Abozaid S, van Haaften T, Sawicka M, Eaton F, Chen M, Thebaud B. Adrenomedullin promotes lung angiogenesis, alveolar development and repair. Am J Respir Cell Mol Biol 43: 152‐152, 2010.
 381. Van Der Heijden M, van Nieuw Amerongen GP, Koolwijk P, van Hinsbergh VW, Groeneveld AB. Angiopoietin‐2, permeability oedema, occurrence and severity of ALI/ARDS in septic and non‐septic critically ill patients. Thorax 63: 903‐903, 2008.
 382. Varet J, Douglas SK, Gilmartin L, Medford AR, Bates DO, Harper SJ, Millar AB. VEGF in the lung: A role for novel isoforms. Am J Physiol Lung Cell Mol Physiol 298: L768‐L774, 2010.
 383. Varet J, Douglas SK, Gilmartin L, Medford ARL, Bates DO, Harper SJ, Millar AB. VEGF in the lung: A role for novel isoforms. Am J Physiol Lung Cell Mol Physiol 298: L768‐L774, 2010.
 384. Verloop MC. On the arteriae bronchiales and their anastomosing with the arteria pulmonalis in some rodents; a micro‐anatomical study. Acta Anat (Basel) 7: 1‐1, 1949.
 385. Vincent J, Hellot MF, Vargas E, Gautier H, Pasquis P, Lefrancois R. Pulmonary gas exchange, diffusing capacity in natives and newcomers at high altitude. Respir Physiol 34: 219‐219, 1978.
 386. Voelkel NF, Douglas IS, Nicolls M. Angiogenesis in chronic lung disease. Chest 131: 874‐874, 2007.
 387. Voswinckel R, Motejl V, Fehrenbach A, Wegmann M, Mehling T, Fehrenbach H, Seeger W. Characterisation of post‐pneumonectomy lung growth in adult mice. Eur Respir J 24: 524‐524, 2004.
 388. Wagenvoort CA, Wagenvoort N. Arterial anastomoses, bronchopulmonary arteries, and pulmobronchial arteries in perinatal lungs. Lab Invest 16: 13‐13, 1967.
 389. Wagner EM. Bronchial Circulation. In: Crystal RG, Wea JB, editors. The Lung: Scientific Foundations. Philadelphia: Raven Publishers, 1997, p. 1093‐1093.
 390. Wagner EM, Mitzner W, Brown RH. Site of functional bronchopulmonary anastomoses in sheep. Anat Rec 254: 360‐360, 1999.
 391. Wagner EM, Petrache I, Schofield B, Mitzner W. Pulmonary ischemia induces lung remodeling and angiogenesis. J Appl Physiol 100: 587‐587, 2006.
 392. Wagner EM, Sanchez J, McClintock JY, Jenkins J, Moldobaeva A. Inflammation and ischemia‐induced lung angiogenesis. Am J Physiol Lung Cell Mol Physiol 294: L351‐L357, 2008.
 393. Wagner PD, Gale GE, Moon RE, Torre‐Bueno JR, Stolp BW, Saltzman HA. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J Appl Physiol 61: 260‐260, 1986.
 394. Wagner PD, Sutton JR, Reeves JT, Cymerman A, Groves BM, Malconian MK. Operation Everest II: Pulmonary gas exchange during a simulated ascent of Mt. Everest. J Appl Physiol 63: 2348‐2348, 1987.
 395. Wagner WW Jr, Latham LP. Pulmonary capillary recruitment during airway hypoxia in the dog. J Appl Physiol 39: 900‐900, 1975.
 396. Wagner WW Jr, Latham LP, Hanson WL, Hofmeister SE, Capen RL. Vertical gradient of pulmonary capillary transit times. J Appl Physiol 61: 1270‐1270, 1986.
 397. Walter DH, Haendeler J, Reinhold J, Rochwalsky U, Seeger F, Honold J, Hoffmann J, Urbich C, Lehmann R, Arenzana‐Seisdesdos F, Aicher A, Heeschen C, Fichtlscherer S, Zeiher AM, Dimmeler S. Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease. Circ Res 97: 1142‐1142, 2005.
 398. Ward JP, McMurtry IF. Mechanisms of hypoxic pulmonary vasoconstriction and their roles in pulmonary hypertension: New findings for an old problem. Curr Opin Pharmacol 9: 287‐287, 2009.
 399. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 342: 1334‐1334, 2000.
 400. Webb WR, Jacobs RP. Transpleural abdominal systemic artery‐pulmonary artery anastomosis in patients with chronic pulmonary infection. AJR Am J Roentgenol 129: 233‐233, 1977.
 401. Weibel ER. Early stages in the development of collateral circulation to the lung in the rat. Circ Res 8: 353‐353, 1960.
 402. Weibel ER. Understanding the limitation of O2 supply through comparative physiology. Respir Physiol 118: 85‐85, 1999.
 403. Weibel ER, Gomez DM. A principle for counting tissue structures on random sections. J Appl Physiol 17: 343‐343, 1962.
 404. Weibel ER, Hsia CC, Ochs M. How much is there really? Why stereology is essential in lung morphometry. J Appl Physiol 102: 19‐19, 2007.
 405. Weil JV, Stevens T, Pickett CK, Tatsumi K, Dickinson MG, Jacoby CR, Rodman DM. Strain‐associated differences in hypoxic chemosensitivity of the carotid body in rats. Am J Physiol 274: L767‐L774, 1998.
 406. West J, Harral J, Lane K, Deng Y, Ickes B, Crona D, Albu S, Stewart D, Fagan K. Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions. Am J Physiol Lung Cell Mol Physiol 295: L744‐L755, 2008.
 407. West JB. Diffusing capacity of the lung for carbon monoxide at high altitude. J Appl Physiol 17: 421‐421, 1962.
 408. West JB, Hackett PH, Maret KH, Milledge JS, Peters RM Jr, Pizzo CJ, Winslow RM. Pulmonary gas exchange on the summit of Mount Everest. J Appl Physiol 55: 678‐678, 1983.
 409. West JB, Wagner PD. Predicted gas exchange on the summit of Mt. Everest. Respir Physiol 42: 1‐1, 1980.
 410. Wood D, Miller M. Role of dual pulmonary circulation in various pathological conditions of the lungs. J Thoracic Surg 7: 649‐649, 1938.
 411. Woodfin A, Voisin MB, Nourshargh S. PECAM‐1: A multi‐functional molecule in inflammation and vascular biology. Arterioscler Thromb Vasc Biol 27: 2514‐2514, 2007.
 412. Yamaji‐Kegan K, Su Q, Angelini DJ, Champion HC, Johns RA. Hypoxia‐induced mitogenic factor has proangiogenic and proinflammatory effects in the lung via VEGF and VEGF receptor‐2. Am J Physiol Lung Cell Mol Physiol 291: L1159‐L1168, 2006.
 413. Yamaji‐Kegan K, Su Q, Angelini DJ, Johns RA. IL‐4 is proangiogenic in the lung under hypoxic conditions. J Immunol 182: 5469‐5469, 2009.
 414. Yatsunami J, Tsuruta N, Ogata K, Wakamatsu K, Takayama K, Kawasaki M, Nakanishi Y, Hara N, Hayashi S. Interleukin‐8 participates in angiogenesis in non‐small cell, but not small cell carcinoma of the lung. Cancer Lett 120: 101‐101, 1997.
 415. Yildirim AO, Muyal V, John G, Muller B, Seifart C, Kasper M, Fehrenbach H. Palifermin induces alveolar maintenance programs in emphysematous mice. Am J Respir Crit Care Med 181: 705‐705, 2010.
 416. Yoneda J, Kuniyasu H, Crispens MA, Price JE, Bucana CD, Fidler IJ. Expression of angiogenesis‐related genes and progression of human ovarian carcinomas in nude mice. J Natl Cancer Inst 90: 447‐447, 1998.
 417. Yuan A, Yang PC, Yu CJ, Chen WJ, Lin FY, Kuo SH, Luh KT. Interleukin‐8 messenger ribonucleic acid expression correlates with tumor progression, tumor angiogenesis, patient survival, and timing of relapse in non‐small‐cell lung cancer. Am J Respir Crit Care Med 162: 1957‐1957, 2000.
 418. Yuan S, Hannam V, Belcastro R, Cartel N, Cabacungan J, Wang J, Diambomba Y, Johnstone L, Post M, Tanswell AK. A role for platelet‐derived growth factor‐BB in rat postpneumonectomy compensatory lung growth. Pediatr Res 52: 25‐25, 2002.
 419. Zaidi SH, You XM, Ciura S, Husain M, Rabinovitch M. Overexpression of the serine elastase inhibitor elafin protects transgenic mice from hypoxic pulmonary hypertension. Circulation 105: 516‐516, 2002.
 420. Zhai R, Gong MN, Zhou W, Thompson TB, Kraft P, Su L, Christiani DC. Genotypes and haplotypes of the VEGF gene are associated with higher mortality and lower VEGF plasma levels in patients with ARDS. Thorax 62: 718‐718, 2007.
 421. Zhang J, Luo B, Tang L, Wang Y, Stockard CR, Kadish I, Van Groen T, Grizzle WE, Ponnazhagan S, Fallon MB. Pulmonary angiogenesis in a rat model of hepatopulmonary syndrome. Gastroenterology 136: 1070‐1070, 2009.
 422. Zhang Q, Bellotto DJ, Ravikumar P, Moe OW, Hogg RT, Hogg DC, Estrera AS, Johnson RL Jr, Hsia CC. Postpneumonectomy lung expansion elicits hypoxia‐inducible factor‐1alpha signaling. Am J Physiol Lung Cell Mol Physiol 293: L497‐L504, 2007.
 423. Zhang Q, Moe OW, Garcia JA, Hsia CC. Regulated expression of hypoxia‐inducible factors during postnatal and postpneumonectomy lung growth. Am J Physiol Lung Cell Mol Physiol 290: L880‐L889, 2006.
 424. Zhang ZG, Zhang L, Jiang Q, Chopp M. Bone marrow‐derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res 90: 284‐284, 2002.
 425. Zhao L, Brown LA, Owji AA, Nunez DJ, Smith DM, Ghatei MA, Bloom SR, Wilkins MR. Adrenomedullin activity in chronically hypoxic rat lungs. Am J Physiol 271: H622‐H629, 1996.
 426. Zhao YD, Courtman DW, Deng Y, Kugathasan L, Zhang Q, Stewart DJ. Rescue of monocrotaline‐induced pulmonary arterial hypertension using bone marrow‐derived endothelial‐like progenitor cells: Efficacy of combined cell and eNOS gene therapy in established disease. Circ Res 96: 442‐442, 2005.
 427. Zheng H, Dai T, Zhou B, Zhu J, Huang H, Wang M, Fu G. SDF‐1alpha/CXCR4 decreases endothelial progenitor cells apoptosis under serum deprivation by PI3 K/Akt/eNOS pathway. Atherosclerosis 201: 36‐42, 2008.
 428. Ziche M, Maglione D, Ribatti D, Morbidelli L, Lago CT, Battisti M, Paoletti I, Barra A, Tucci M, Parise G, Vincenti V, Granger HJ, Viglietto G, Persico MG. Placenta growth factor‐1 is chemotactic, mitogenic, and angiogenic. Lab Invest 76: 517‐517, 1997.
 429. Ziche M, Morbidelli L, Choudhuri R, Zhang HT, Donnini S, Granger HJ, Bicknell R. Nitric oxide synthase lies downstream from vascular endothelial growth factor‐induced but not basic fibroblast growth factor‐induced angiogenesis. J Clin Invest 99: 2625‐2625, 1997.
 430. Zielonka TM, Demkow U, Filewska M, Bialas‐Chromiec B, Zycinska K, Radzikowska E, Korzeniewska M, Wardyn KA, Kus J, Skopinska‐Rozewska E. Angiogenic activity of sera from silicosis and pulmonary langerhans cell histiocytosis patients in relation to lung function tests. J Physiol Pharmacol 59(Suppl 6): 781‐781, 2008.
 431. Zwemer CF, Song MY, Carello KA, D'Alecy LG. Strain differences in response to acute hypoxia: CD‐1 versus C57 BL/6 J mice. J Appl Physiol 102: 286‐286, 2007.

Related Articles:

Endothelial Cell Energy Metabolism, Proliferation, and Apoptosis in Pulmonary Hypertension
Experimental and Transgenic Models of Pulmonary Hypertension
Hypoxic Pulmonary Hypertension of the Newborn
Right Ventricle in Pulmonary Hypertension
Smooth Muscle Cell Hypertrophy, Proliferation, Migration and Apoptosis in Pulmonary Hypertension
Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling
Gas Exchange in Hypoxia, Apnea, and Hyperoxia
Physiology of Extreme Altitude

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Paul McLoughlin, Michael P. Keane. Physiological and Pathological Angiogenesis in the Adult Pulmonary Circulation. Compr Physiol 2011, 1: 1473-1508. doi: 10.1002/cphy.c100034