Comprehensive Physiology Wiley Online Library

Physiology and Pathobiology of Microvascular Endothelium

Full Article on Wiley Online Library


The sections in this article are:

1 Microvascular ECs: Morphological Features and Markers
2 Physiological Functions of ECs at Rest
3 Type I Activation of Endothelium
4 Type II Activation of ECs
5 Immune‐Mediated Activation of ECs
6 Endothelial Dysfunction, Injury and Cytoprotection
7 ECs and Chronic Inflammation
8 Summary
 1. Aird WC. Phenotypic heterogeneity of the endothelium: 1. Structure, function, and mechanisms. Circ Res 100: 158–173, 2007.
 2. Aird WC. Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ Res 100: 174–190, 2007.
 3. Gotlieb AI. The endothelial cytoskeleton: organization in normal and regenerating endothelium. Toxicol Pathol 18: 603–617, 1990.
 4. Girard PR and Nerem RM. Shear stress modulates endothelial cell morphology and F‐actin organization through the regulation of focal adhesion‐associated proteins, J Cell Physiol 163: 179–193, 1995.
 5. Rogers KA, McKee NH, et al. Preferential orientation of centrioles toward the heart in endothelial cells of major blood vessels is reestablished after reversal of a segment. Proc Natl Acad Sci USA 82: 3272–3276, 1985.
 6. Imcke E, Ruszczak Z, et al. Cultivation of human dermal microvascular endothelial cells in vitro: immunocytochemical and ultrastructural characterization and effect of treatment with three synthetic retinoids. Arch Dermatol Res 283: 149–157, 1991.
 7. Katagata Y, Takeda H, et al. Occurrence and comparison of the expressed keratins in cultured human fibroblasts, endothelial cells and their sarcomas. J Dermatol Sci 30: 1–9, 2002.
 8. Palade GE and Bruns RR. Structural modulations of plasmalemmal vesicles. J Cell Biol 37: 633–649, 1968.
 9. Liu J and Schnitzer JE. Analysis of lipids in caveolae. Methods Mol Biol 116: 61–72, 1999.
 10. Frank PG, Woodman SE, et al. Caveolin, caveolae, and endothelial cell function. Arterioscler Thromb Vasc Biol 23: 1161–1168, 2003.
 11. Weibel ER and Palade GE. New cytoplasmic components in arterial endothelia. J Cell Biol 23: 101–112, 1964.
 12. Ewenstein BM, Warhol MJ, et al. Composition of the von Willebrand factor storage organelle (Weibel‐Palade body) isolated from cultured human umbilical vein endothelial cells. J Cell Biol 104: 1423–1433. 1987.
 13. Bazzoni G and Dejana E. Endothelial cell‐to‐cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84: 869–901, 2004.
 14. Segal SS. Regulation of blood flow in the microcirculation. Microcirculation 12: 33–45, 2005.
 15. Eichmann A, Li Y, et al. Vascular development: from precursor cells to branched arterial ad venous networks. Int J Dev Biol 49: 259–267, 2005.
 16. Jaffredo T, Nottingham W, et al. From hemangioblast to hematopoietic stem cell: an endothelial connection? Exp Hematol 33: 1029–1040, 2005.
 17. Hristov M and Weber C. Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance. J Cell Mol Med 8: 498–508, 2004.
 18. Yoder MC, Mead LE, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 109: 1801–1809, 2007.
 19. Perez‐Pomares JM, Carmona R, et al. Origin of coronary endothelial cells from epicardial mesothelium in avian embryos. Int J Dev Biol 46: 1005–1013, 2002.
 20. Rossant J and Howard L. Signaling pathways in vascular development. Annu Rev Cell Dev Biol 18: 541–573, 2002.
 21. Huddleson JP, Srinivasan S, et al. Fluid shear stress induces endothelial KLF2 gene expression through a defined promoter region. Biol Chem 385: 723–729, 2004.
 22. SenBanerjee S, Lin Z, et al. KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation. J Exp Med 199: 1305–1315, 2004.
 23. Chachisvilis M, Zhang YL, et al. G protein‐coupled receptors sense fluid shear stress in endothelial cells. Proc Natl Acad Sci USA 103: 15463–15468, 2006.
 24. Tzima E, Irani‐Tehrani M, et al. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437: 426–431, 2005.
 25. Wang Y, Miao H, et al. Interplay between integrins and FLK‐I in shear stress‐induced signaling. Am J Physiol Cell Physiol 283: C1540–CC1547, 2002.
 26. Davis GE and Senger DR. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res 97: 1093–1107, 2005.
 27. Sixma JJ and de Groot PG. von Willebrand factor and the blood vessel wall. Mayo Clin Proc 66: 628–633. 1991.
 28. Vorbrodt AW and Dobrogowska DH. Molecular anatomy of intercellular junctions in brain endothelial and epithelial barriers: electron microscopist's view. Brain Res Brain Res Rev 42: 221–242, 2003.
 29. Minshall RD and Malik AB. Transport across the endothelium: regulation of endothelial permeability. Handb Exp Pharmacol 176 (Pt 1): 107–144, 2006.
 30. Rippe B, Rosengren BI. et al. Transendothelial transport: the vesicle controversy. J Vasc Res 39: 375–390, 2002.
 31. Politz O, Gratchev A, et al. Stabilin‐1 and ‐2 constitute a novel family of fasciclin‐like hyaluronan receptor homologues. Biochem J 362: 155–164, 2002.
 32. Esser S, Wolburg K, et al. Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 140: 947–959, 1998.
 33. Ballermann BJ. Glomerular endothelial cell differentiation. Kidney Int 67: 1668–1671, 2005.
 34. Stan RV. Kubitza M, et al. PV‐1 is a component of the fenestral and stomatal diaphragms in fenestrated endothelia. Proc Natl Acad Sci USA 96: 13203–13207, 1999.
 35. Janzer RC and Raff MC, Astrocytes induce blood‐brain barrier properties in endothelial cells. Nature 325: 253–257, 1987.
 36. Hart TK and Pino RM. Pseudoislet vascularization. Induction of diaphragm‐fenestrated endothelial from the hepatic sinusoids. Lab Invest 54: 304–313, 1986.
 37. Milici AJ, Furie MB, et al. The formation of fenestrations and channels by capillary endothelium in vitro. Proc Natl Acad Sci USA 82: 6181–6185, 1985.
 38. Svensjo E and Grega GJ. Evidence for endothelial cell‐mediated regulation of macromolecular permeability by postcapillary venules. Fed Proc 45: 89–95, 1986.
 39. Cohnheim J. Lectures in General Pathology (Translated by AD McKee from the Second German Edition 1). London: New Syndenham Society, 1989.
 40. Messadi DV, Pober JS. et al. Induction of an activation antigen on postcapillary venular endothelium in human skin organ culture. J Immunol 139: 1557–1562, 1987.
 41. Simionescu M, Simionescu N, et al. Segmental differentiations of cell junctions in the vascular endothelium. The microvasculature. J Cell Biol 67: 863–885, 1975.
 42. Heltranu C, Simionescu M, et al. Histamine receptors of the microvascular endothelium revealed In situ with a histamine‐ferritin conjugate: characteristic high‐affinity binding sites in venules. J Cell Biol 93: 357–364, 1982.
 43. Braverman IM. Ultrastructure and organization of the cutaneous microvasculature in normal and pathologic states. J Invest Dermatol 93: 2S–9S, 1989.
 44. Petzelbauer P, Pober JS, et al. Inducibility and expression of microvascular endothelial adhesion molecules in lesional, perilesional, and uninvolved skin of psoriatic patients. J Invest Dermatol 103: 300–305, 1994.
 45. Phillips GD, Whitehead RA, et al. Initiation and pattern of angiogenesis in wound healing in the rat. Am J Anat 192: 257–262, 1991.
 46. Stupack DG and Cheresh DA. Integrins and angiogenesis. Curr Top Dev Biol 64: 207–238, 2004.
 47. Cueni LN and Detmar M. New insights into the lymphatic vascular system and its role in disease. J Invest Dermatol 126: 2167–2177, 2006.
 48. Drayton DL, Liao S, et al. Lymphoid organ development: from ontogeny to neogenesis. Nat Immunol 7: 344–353, 2006.
 49. Hajitou A, Pasqualini R, et al. Vascular targeting: recent advances and therapeutic perspectives. Trends Cardiovasc Med 16: 80–88, 2006.
 50. Amout J, Hoylaerts MF, et al. Haemostasis. Handb Exp Pharmacol 176 (II): 1–42, 2006.
 51. Busse R and Fleming I. Vascular endothelium and blood flow. Handb Exp Pharmacol 176 (II): 43–78, 2006.
 52. Brandes RP, Schmitz‐Winnenthal FH, et al. An endothelium‐derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium‐dependent vasodilator in resistance vessels of wild‐type and endothelial NO synthase knockout mice. Proc Natl Acad Sci USA 97: 9747–9752, 2000.
 53. Moncada S. Nitric oxide and the vascular endothelium. Handb Exp Pharmacol 176/I: 213–254, 2006.
 54. McVerry BJ and Garcia JG. Endothelial cell barrier regulation by sphingosine l‐phosphate. J Cell Biochem 92: 1075–1085, 2004.
 55. Feng D, Nagy JA, et al. Vesiculo‐vaculoar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine and serotonin. J Exp Med 59: 100–115, 1996.
 56. Ley K and Reutershen J. Leukocyte‐endothelial interactions in health and disease. Handb Exp Pharmacol 176/II: 97–133, 2006.
 57. De Caterina R, Libby P, et al. Nitric oxide decreases cytokine‐induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 96: 60–68, 1995.
 58. Kuhlencordt PJ, Rosel E, et al. Role of endothelial nitric oxide synthase in endothelial activation: insights from eNOS knockout endothelial cells. Am J Physiol Cell Physiol 286: C1195–1202, 2004.
 59. Tran QK and Watanabe H. Calcium signalling in the endothelium. Handb Exp Pharmacol 176 (Pt 1): 145–187, 2006.
 60. Luckhoff A and Clapham DE. Inositol 1,3,4,5‐tetrakisphosphate activates an endothelial Ca(2+)‐permeable channel. Nature 355: 356–358, 1992.
 61. Egan K and FitzGerald GA. Eicosanoids and the vascular endothelium. Handb Exp Pharmacol 176 (1): 189–211, 2006.
 62. Birch KA, Ewenstein BM, et al. Prolonged peak elevations in cytoplasmic free calcium ions, derived from intracellular stores, correlate with the extent of thrombin‐stimulated exocytosis in single human umbilical vein endothelial cells. J Cell Physiol 160: 545–554, 1994.
 63. Matsushita K, Morrell CN, et al. Nitric oxide regulates exocytosis by S‐nitrosylation of N‐ethylmaleimide‐sensitive factor. Cell 115: 139–150, 2003.
 64. Lorant DE. Patel KD, et al. Coexpression of GMP‐140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils. J Cell Biol 115; 223–234, 1991.
 65. Sugama Y, Tiruppathi C, et al. Thrombin‐induced expression of endothelial P‐selectin and intercellular adhesion molecule‐1: a mechanism for stabilizing neutrophil adhesion. J Cell Biol 119: 935–944, 1992.
 66. Lou O, Alcaide P, et al. CD99 is a key mediator of the transendothelial migration of neutrophils. J Immunol 178: 1136–1143, 2007.
 67. Frangogiannis NG. Targeting the inflammatory response in healing myocardial infarcts. Curr Med Chem 13: 1877–1893, 2006.
 68. Stevens T, Garcia JG, et al. Mechanisms regulating endothelial cell barrier function. Am J Physiol Lung Cell Mol Physiol 279: L419–1422, 2000.
 69. Birukova AA, Birukov KG, et al. Novel role of microtubules in thrombin‐induced endothelial barrier dysfunction. FASEB J 18: 1879–1890, 2004.
 70. Gorovoy M, Niu J, et al. LIM kinase 1 coordinates microtubule stability and actin polymerization in human endothelial cells. J Biol Chem 280: 26533–26542, 2005.
 71. Le J and Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest 56: 234–248, 1987.
 72. Fossiez F, Djossou O, et al. T cell interieukin‐17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 183: 2593–2603, 1996.
 73. Pober JS. Tumor necrosis factor. In Arid WC (ed), Edothelial Biomedicine, Cambridge University Press, Cambridge p. 261–265, 2007.
 74. D'Alessio A, Al‐Lamki RS, et al. Caveolae participate in tumor necrosis factor receptor 1 signaling and internalization in a human endothelial cell line. Am J Pathol 166: 1273–1282, 2005.
 75. Jones SJ, Ledgerwood EC, et al. TNF recruits TRADD to the plasma membrane but not the trans‐Golgi network, the principal subcellular location of TNF‐RI. J Immunol 162: 1042–1048, 1999.
 76. Wertz IE, O'Rourke KM, et al. De‐ubiquitination and ubiquitin ligase domains of A20 downregulate NF‐kappaB signalling. Nature 430: 694–699, 2004.
 77. Yaron A, Hatzubai A, et al. Identification of the receptor component of the IkappaBalpha‐ubiquitin ligase. Nature 396: 590–594, 1998.
 78. Zhong H, May MJ, et al. The phosphorylation status of nuclear NF‐kappa B determines its association with CBP/p300 or HDAC‐1. Mol Cell 9: 625–636, 2002.
 79. Zhang, R H Zhang, et al (2007). RIP1‐mediated AIP1 phosphorylation at a 14‐3‐3 binding site is critical for TNF‐induced ASK1‐JNK/p38 activation. J Biol Chem: 282: 14788–14796. 2007.
 80. Zhang H, Zhang R, et al. AIP1/DAB21P, a novel member of the RasGAP family, transduces TRAF2‐induced ASK1‐JNK activation. J Biol Chem 279: 44955–44965, 2004.
 81. De Luca LG, Johnson DR, et al. cAMP and tumor necrosis factor competitively regulate transcriptional activation through and nuclear factor binding to the cAMP‐responsive element/activating transcription factor element of the endothelial leukocyte adhesion molecule‐1 (E‐selectin) promoter. J Biol Chem 269: 19193–19196, 1994.
 82. Karmann K, Min W, et al. Activation and homologous desensitization of human endothelial cells by CD40 ligand, tumor necrosis factor, and interleukin 1. J Exp Med 184: 173–182, 1996.
 83. Kluger MS, Johnson DR, et al. Mechanism of sustained E‐selectin expression in cultured human dermal microvascualr endothelial cells. J Immunol 158: 887–896, 1997.
 84. Li X and Qin J. Modulation of Toll‐interieukin 1 receptor mediated signaling. J Mol Med 83: 258–266. 2005.
 85. Rosenkranz‐Weiss P, Sessa WC, et al. Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity. J Clin Invest 93: 2236–2243, 1994.
 86. Yoshizumi M, Perrella M, et al. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half‐life. Circ Res 73: 205–209. 1993.
 87. Pan J, Xia L, et al. Comparison of promoters for the murine and human P‐selectin genes suggests species‐specific and conserved mechanisms for transcriptional regulation in endothelial cells. J Biol Chem 273: 10058–10067. 1998.
 88. Zavoico GB. Ewenstein BM, et al. IL‐1 and related cytokines enhance thrombin‐stimulated PGI2 production in cultured endothelial cells without affecting thrombin‐stimulated von Willebrand factor secretion or platelet‐activating factor biosynthesis. J Immunol 142; 3993–3999, 1989.
 89. Kunkel SL, Lukacs N, et al. Expression and biology of neutropohil and endothelial cell‐derived chemokines. Semin Cell Biol 6: 327–336, 1995.
 90. Webb LM, Ehrengruber MU, et al. Binding to heparan sulfate or heparin enhances neutrophil responses to interiukin 8. Proc Natl Acad Sci USA 90: 7158–7162, 1993.
 91. Briscoe DM, Cotran RS, et al. Effects of tumor necrosis factor, lipopolysaccharide, and IL‐4 on the expression of vascular cell adhesion molecule‐1 in vivo. Correlation with CD3+ T cell infiltration. J Immunol 149: 2954–2960, 1992.
 92. Collins T, Read MA, et al. Transcriptional regulation of endothelial cell adhesion molecules: NF‐kappa B and cytokine‐inducible enhancers. FASEB J 9: 899–909. 1995.
 93. Muller WA. Leukocyte‐endothelial‐cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol 224: 327–334, 2003.
 94. Stolpen AH, Guinan EC, et al. Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human vascular endothelial cell monolayers. Am J Pathol 123: 16–24, 1986.
 95. Wojciak‐Stothard B, Entwistle A, et al. Regulation of TNF‐alpha‐induced reorganization of the actin cytoskeleton and cell‐cell junctions by Rho, Rac, and Cdc42 in human endothelial cells. J Cell Physiol 176: 150–165, 1998.
 96. Clark PR, Manes TD, et al. An inflammatory pathway of interferon‐γ production in coronary atherosclerosis, J Immunol 178: 592–604. 2007.
 97. Petrache I, Birukova A, et al. The role of the microtubules in tumor necrosis factor‐alpha‐induced endothelial cell permeability. Am J Respir Cell Mol Biol 28: 574–581, 2003.
 98. Lentz SR. Tsiang M, et al. Regulation of thrombomodulin by tumor necrosis factor‐alpha: comparison of transcriptional and posttranscriptional mechanisms. Blood 77: 542–550, 1991.
 99. Lowenstein CJ, Morrell CN, et al. Regulation of Weibel‐Palade body exocytosis. Trends Cardiovasc Med 15: 302–328, 2005.
 100. Bevilacqua MP, Pober JS, et al. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin I. Proc Natl Acad Sci USA 83: 4533–4537, 1986.
 101. Bavendiek U, Libby P, et al. Induction of tissue factor expression in human endothelial cells by CD40 ligand is mediated via activator protein 1, nuclear factor kappa B, and Egr‐1. J Biol Chem 277: 25032–25039, 2002.
 102. Ghanekar A, Mendicino M, et al. Endothelial induction of fg12 contributes to thrombosis during acute vascular xenograft rejection. J Immunol 172: 5693–5701, 2004.
 103. Rothstein JL and Schreiber H. Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice. Proc Natl Acad Sci USA 85: 607–611, 1988.
 104. Farrar JD, Asnagli H, et al. T helper subset development: roles of instruction, selection, and transcription, J Clin Invest 109: 431–435, 2002.
 105. Doukas J and Pober JS. IFN‐γ enhances endothelial activation induced by TNF but not IL‐1. J Immunol 145: 1727–1733, 1990.
 106. Lechleitner S, Gille J, et al. Interferon enhances tumor necrosis factor‐induced vascular cell adhesion molecule I (CD 106) expression in human endothelial cells by an interferon‐related factor 1‐dependent pathway. J Exp Med 187: 2023–2030, 1998.
 107. Moser B, Loetscher M, et al. Lymphocyte responses to chemokines. Int Rev Immunol 16: 323–344, 1998.
 108. Tellides G and Pober JS. The interferon‐γ axis in graft arteriosclerosis. Circ Res 100: 622–632, 2007.
 109. Sallusto F, Geginat J, et al. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22: 745–763, 2004.
 110. Schroder K, Hertzog PJ, et al. Interferon‐gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75: 163–189, 2004.
 111. Choy JC, Wang Y, et al. Induction of inducible NO synthase in bystander human T cells increases allogeneic responses in the vasculature. Proc Natl Acad Sci USA 104: 1313–1318, 2007.
 112. Palmer‐Crocker RL and Pober JS. IL‐4 induction of VCAM‐1 on endothelial cells involves activation of a protein tyrosine kinase. J Immunol 154: 2838–2845, 1995.
 113. Palmer‐Crocker RL, Hughes CC, et al. IL‐4 and IL‐13 activate the JAK2 tyrosine kinase and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the gamma c chain. J Clin Invest 98: 604–609. 1996.
 114. Afzali B, Lombardi G, et al. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease, Clin Exp Immunol 148: 32–46, 2007.
 115. Belizna C, Duijvestijn A, et al. Antiendothelial cell antibodies in vasculitis and connective tissue disease. Ann Rheum Dis 65: 1545–1550, 2006.
 116. Yamakuchi M, Kirkiles‐Smith NC, et al. Antibody to human leukocyte antigen triggers endothelial exocytosis. Proc Natl Acad Sci USA 104: 1301–1306, 2007.
 117. Lawson C, Holder AL, et al. Anti‐intercellular adhesion molecule‐1 antibodies in sera of heart transplant recipients: a role in endothelial cell activation. Transplantation 80: 264–271, 2005.
 118. Smith JD, Yacoub MH, et al. Endothelial cell activation by sera containing HAL antibodies is mediated by interieukin‐1. Transplant 6: 1229–1237, 1998.
 119. Albrecht EA, Chinnaiyan AM, et al. C5a‐induced gene expression in human umbilical vein endothelial cells. Am J Pathol 164: 849–859, 2004.
 120. Hamilton KK, Hatlori R, et al. Complement proteins C5b‐9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. J Biol Chem 265: 3809–3814, 1990.
 121. Piatt JL, Dalmasso AP, et al. The role of C5a and antibody in the release of heparan sulfate from endothelial cells. Eur J Immunol 21: 2887–2890, 1991.
 122. Choi J, Enis D, et al. T lymphocyte‐endothelial cell interactions. Ann Rev Immunol 22, 2004.
 123. Murakami K, Ma W, et al. Human endothelial cells augment early CD40 ligand expression in activated CD4+ T cells through LFA‐3‐mediated stabilization of mRNA. J Immunol 163: 2667–2673, 1999.
 124. Kummer M, Lev A, et al. Vascular endothelial cells have impaired capacity to present immunodominant, antigenic peptides: a mechanism of cell type‐specific immune escape. J Immunol 174: 1947–1953, 2005.
 125. Pober, J S, and W. Min ( 2006). Endothelial Cell Dysfunction. Injury and Death. Handbook of Experimental Pharmacology. H. A. Moncada S. Berlin. Springer‐Verlag. 176/II: 135–156.
 126. Warnholtz A, Wendt M, et al. Clinical aspects of reactive oxygen and nitrogen species. Biochem Soc Symp : 121–133, 2004.
 127. Bombeli T, Karsan A, et al. Apoptotic vascular endothelial cells become procoagulant. Blood 89: 2429–2442, 1997.
 128. Waxman AB. Mahboubi K, et al. Interieukin‐11 and interleukin‐6 protect cultured human endothelial cells from H202‐induced cell death. Am J Respir Cell Mol Biol 29: 513–522, 2003.
 129. Kirkiles‐Smith NC, Mahboubi K, et al. IL‐11 protects human microvascular endothelium from alloinjury in vivo by induction of survivin expression, J Immunol 172: I391–I396, 2004.
 130. Shaffer JB, Treanor CP, et al. Expression of bovine and mouse endothelial cell antioxidant enzymes following TNF‐alpha exposure. Free Radic Biol Med 8: 497–502, 1990.
 131. Otterbein LE, Soares MP, et al. Heme oxygenase‐1: unleashing the protective properties of heme. Trends Immunol 24: 449–455, 2003.
 132. Ryter SW and Choi AM. Cytoprotective and anti‐inflammatory actions of carbon monoxide in organ injury and sepsis models. Novartis Found Symp 280: 165–175, 2007, Discussion 175‐81.
 133. Bach FH, Hancock WW, et al. Protective genes expressed in endothelial cells: a regulatory response to injury. Immunol Today 18: 483–486, 1997.
 134. Fischer C, Schneider M, et al. Principles and therapeutic implications of angiogenesis, vasculogenesis and arteriogenesis. Handb Exp Pharmacol 176 (11): 157–212, 2006.
 135. Hofer E and Schweighofer B. Signal transduction induced in endothelial cells by growth factor receptors involved in angiogenesis. Thromb Haemost 97: 355–363, 2007.
 136. Morisada T, Kubota Y, et al. Angiopoietins and angiopoietin‐like proteins in angiogenesis. Endothelium 13: 71–79, 2006.
 137. Pober JS and Sessa WS. Evolving functions of endothelial cells in inflammation. Nature Rev Immunol 7: 803–815, 2007.
 138. Mehrad B, Keane MP, et al. Chemokines as mediators of angiogenesis. Thromb Haemost 97: 755–762, 2007.
 139. Baffert F, Le T, et al. Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am J Physiol Heart Circ Physiol 290: H547–5559, 2005.
 140. Pober JS and Cotran RS. The role of endothelial cells in inflammation. Transplantation 50: 537–544, 1990.
 141. Manes T and Pober JS. Antigen presentation by human dermal microvascular endothelial cells triggers ICAM‐1‐dependent tansendothelial protrusion by and fractalkine‐dependent transendothelial migration of effector memory CD4+ T cells. J Immunol (in press).

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Jordan S. Pober. Physiology and Pathobiology of Microvascular Endothelium. Compr Physiol 2011, Supplement 9: Handbook of Physiology, The Cardiovascular System, Microcirculation: 37-55. First published in print 2008. doi: 10.1002/cphy.cp020402