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Right Ventricle in Pulmonary Hypertension

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Abstract

During heart development chamber specification is controlled and directed by a number of genes and a fetal heart gene expression pattern is revisited during heart failure . In the setting of chronic pulmonary hypertension the right ventricle undergoes hypertrophy, which is likely initially adaptive, but often followed by decompensation, dilatation and failure. Here we discuss differences between the right ventricle and the left ventricle of the heart and begin to describe the cellular and molecular changes which characterize right heart failure. A prevention and treatment of right ventricle failure becomes a treatment goal for patients with severe pulmonary hypertension it follows that we need to understand the pathobiology of right heart hypertrophy and the transition to right heart failure. © 2011 American Physiological Society. Compr Physiol 1:525‐540, 2011.

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Figure 1. Figure 1.

The linear heart tube loops and gives rise to the ventricular and atrial chambers. The cardiac cushions give rise to the cardiac valves. The two ventricles grow independently under the control of an intricate interplay of chamber‐specific transcription factors. RV = right ventricle, LV = left ventricle. Adapted from Olson, with permission .

Figure 2. Figure 2.

The shape of the normal adult right ventricle (RV). The lines drawn to highlight contours can be visualized using a two‐dimensional echocardiogram show a crescentic shape (left). The three‐dimensional echocardiogram shows a more complicated structure. The ellipsoid lines indicate the RV‐inflow and outflow sites and the tricuspid and pulmonary valve planes. Image courtesy of Dr. Florence Sheehan, University of Washington, Seattle.

Figure 3. Figure 3.

Compared are the response of the normal right ventricle (RV) and left ventricle (LV) to an acute increase in the afterload. For a comparable acute rise of the pulmonary artery and aortic pressure the RV stroke volume drops more than that in the LV. Reproduced from Haddad, with permission .

Figure 4. Figure 4.

Mechanisms of activation of PI3K/Akt signaling in response to binding of IGF‐1 or insulin to their membrane tyrosine kinase receptors. Activation of Akt leads to activation of mTOR (molecular target of rapamycin) a central regulator of protein synthesis. Akt also phosphorylates and inhibits the kinase glycogen synthase kinase (GSK‐3). Reproduced from Dorn et al., with permission .

Figure 5. Figure 5.

Tracing of right ventricular systolic pressure obtained after catheterization of a rat subjected to pulmonary artery banding (PAB) and 4 weeks of exposure to chronic hypoxia. In spite of the high RV pressure, the heart does not fail. Reproduced from Bogaard et al., with permission .

Figure 6. Figure 6.

Illustration of the hemodynamic data which characterize the severe pulmonary arterial hypertension and the degree of right heart failure in the Su5416/chronic hypoxia rat model (RVSP = right ventricular systolic pressure, MSAP = mean systolic arterial pressure, CO = cardiac output, RV/LV + S = right ventricle/left ventricle + septum weight, E = early, 3 weeks, L = late, 5 weeks of study protocol). Reproduced from Oka et al., with permission .

Figure 7. Figure 7.

Human right ventricular shape variability obtained via three‐dimensional echocardiography. (Courtesy of Dr. Florence Sheehan, University of Washington, Cardiology Division). The circular or oval green lines delineate right ventricle (RV) inflow and outflow, respectively.

Figure 8. Figure 8.

Confocal microscopy of right ventricle (RV) myocardium of a normal rat and of an animal with SU5416/chronic hypoxia‐induced chronic RV failure. The image obtained after in vivo labeling of endothelial cells with tomato lectin shows significant loss or rarefaction of microvessels in failing RV. Reproduced from Bogaard et al., with permission .

Figure 9. Figure 9.

In the model of chronic right ventricle failure (SU5416/chronic hypoxia) there is a dramatic induction of atrial natriuretic protein (ANP) gene expression is comparison to the change observed in the matched, non‐failing left ventricle. Unpublished data, see reference .

Figure 10. Figure 10.

The flow diagram presents, admittedly in a speculative manner, the pathobiologically important elements as connected sequential steps, starting either with a “pure” diffuse lung tissue damage (emphysema) or a “pure” mechanical cardiac stress due to sustained left heart workload and wall stress increase (e.g., aortic banding). Given the chronicity a combination of diastolic and contractile cardiac dysfunction develops in both situations. *Although the association of pulmonary hypertension and diastolic dysfunction is well recognized, causality—as indicated by the arrows—has not been proposed. EMP = endothelial cell microparticles.

Figure 11. Figure 11.

This schematic illustrates the concept that RV failure can be distinguished from compensated RV hypertrophy and RV decompensation by the loss of the RV microcirculation which may be caused by a loss of expression of critically important angiogenesis (vessel maintenance) factors. EMT = endothelial mesenchymal transition .



Figure 1.

The linear heart tube loops and gives rise to the ventricular and atrial chambers. The cardiac cushions give rise to the cardiac valves. The two ventricles grow independently under the control of an intricate interplay of chamber‐specific transcription factors. RV = right ventricle, LV = left ventricle. Adapted from Olson, with permission .



Figure 2.

The shape of the normal adult right ventricle (RV). The lines drawn to highlight contours can be visualized using a two‐dimensional echocardiogram show a crescentic shape (left). The three‐dimensional echocardiogram shows a more complicated structure. The ellipsoid lines indicate the RV‐inflow and outflow sites and the tricuspid and pulmonary valve planes. Image courtesy of Dr. Florence Sheehan, University of Washington, Seattle.



Figure 3.

Compared are the response of the normal right ventricle (RV) and left ventricle (LV) to an acute increase in the afterload. For a comparable acute rise of the pulmonary artery and aortic pressure the RV stroke volume drops more than that in the LV. Reproduced from Haddad, with permission .



Figure 4.

Mechanisms of activation of PI3K/Akt signaling in response to binding of IGF‐1 or insulin to their membrane tyrosine kinase receptors. Activation of Akt leads to activation of mTOR (molecular target of rapamycin) a central regulator of protein synthesis. Akt also phosphorylates and inhibits the kinase glycogen synthase kinase (GSK‐3). Reproduced from Dorn et al., with permission .



Figure 5.

Tracing of right ventricular systolic pressure obtained after catheterization of a rat subjected to pulmonary artery banding (PAB) and 4 weeks of exposure to chronic hypoxia. In spite of the high RV pressure, the heart does not fail. Reproduced from Bogaard et al., with permission .



Figure 6.

Illustration of the hemodynamic data which characterize the severe pulmonary arterial hypertension and the degree of right heart failure in the Su5416/chronic hypoxia rat model (RVSP = right ventricular systolic pressure, MSAP = mean systolic arterial pressure, CO = cardiac output, RV/LV + S = right ventricle/left ventricle + septum weight, E = early, 3 weeks, L = late, 5 weeks of study protocol). Reproduced from Oka et al., with permission .



Figure 7.

Human right ventricular shape variability obtained via three‐dimensional echocardiography. (Courtesy of Dr. Florence Sheehan, University of Washington, Cardiology Division). The circular or oval green lines delineate right ventricle (RV) inflow and outflow, respectively.



Figure 8.

Confocal microscopy of right ventricle (RV) myocardium of a normal rat and of an animal with SU5416/chronic hypoxia‐induced chronic RV failure. The image obtained after in vivo labeling of endothelial cells with tomato lectin shows significant loss or rarefaction of microvessels in failing RV. Reproduced from Bogaard et al., with permission .



Figure 9.

In the model of chronic right ventricle failure (SU5416/chronic hypoxia) there is a dramatic induction of atrial natriuretic protein (ANP) gene expression is comparison to the change observed in the matched, non‐failing left ventricle. Unpublished data, see reference .



Figure 10.

The flow diagram presents, admittedly in a speculative manner, the pathobiologically important elements as connected sequential steps, starting either with a “pure” diffuse lung tissue damage (emphysema) or a “pure” mechanical cardiac stress due to sustained left heart workload and wall stress increase (e.g., aortic banding). Given the chronicity a combination of diastolic and contractile cardiac dysfunction develops in both situations. *Although the association of pulmonary hypertension and diastolic dysfunction is well recognized, causality—as indicated by the arrows—has not been proposed. EMP = endothelial cell microparticles.



Figure 11.

This schematic illustrates the concept that RV failure can be distinguished from compensated RV hypertrophy and RV decompensation by the loss of the RV microcirculation which may be caused by a loss of expression of critically important angiogenesis (vessel maintenance) factors. EMT = endothelial mesenchymal transition .

References
 1. Abduch MC, Assad RS, Rodriguez MQ, Valente AS, Andrade JL, Demarchi LM, Marcial MB, Aiello VD. Reversible pulmonary trunk banding III: Assessment of myocardial adaptive mechanisms‐contribution of cell proliferation. J Thorac Cardiovasc Surg 133: 1510‐1516, 2007.
 2. Abraham WT, Cheng ML, Smoluk G. Clinical and hemodynamic effects of nesiritide (B‐type natriuretic peptide) in patients with decompensated heart failure receiving beta blockers. Congest Heart Fail 11: 59‐64, 2005.
 3. Abraham WT, Raynolds MV, Badesch DB, Wynne KM, Groves BM, Roden RL, Robertson AD, Lowes BD, Zisman LS, Voelkel NF, Bristow MR, Perryman MB. Angiotensin‐converting enzyme DD genotype in patients with primary pulmonary hypertension: Increased frequency and association with preserved haemodynamics. J Renin Angiotensin Aldosterone Syst 4: 27‐30, 2003.
 4. Achcar RO, Yung GL, Saffer H, Cool CD, Voelkel NF, Yi ES. Morphologic changes in explanted lungs after prostacyclin therapy for pulmonary hypertension. Eur J Med Res 11: 203‐207, 2006.
 5. Adamcova M, Sterba M, Simunek T, Potacova A, Popelova O, Gersl V. Myocardial regulatory proteins and heart failure. Eur J Heart Fail 8: 333‐342, 2006.
 6. Adnot S, Chabrier PE, Andrivet P, Viossat I, Piquet J, Brun‐Buisson C, Gutkowska Y, Braquet P. Atrial natriuretic peptide concentrations and pulmonary hemodynamics in patients with pulmonary artery hypertension. Am Rev Respir Dis 136: 951‐956, 1987.
 7. Aird, W.C. Endothelial Cells in Health and Disease. Boca Raton, London, New York: Taylor and Francis, 2005.
 8. Airhart N, Yang YF, Roberts CT, Jr., Silberbach M. Atrial natriuretic peptide induces natriuretic peptide receptor‐cGMP‐dependent protein kinase interaction. J Biol Chem 278: 38693‐38698, 2003.
 9. Akhavein F, St Michael EJ, Seifert E, Rohlicek CV. Decreased left ventricular function, myocarditis, and coronary arteriolar medial thickening following monocrotaline administration in adult rats. J Apply Physiol 103: 287‐295, 2007.
 10. Andersen CU, Markvardsen LH, Hilberg O, Simonsen U. Pulmonary apelin levels and effects in rats with hypoxic pulmonary hypertension. Respir Med 103: 1663‐1671, 2009.
 11. Andersen JB, Rourke BC, Caiozzo VJ, Bennett AF, Hicks JW. Physiology: Postprandial cardiac hypertrophy in pythons. Nature 434: 37‐38, 2005.
 12. Aurigemma G.P. Diastolic Heart Failure—a common and lethal condition by any name. N Engl J Med 355: 308‐310, 2006.
 13. Bakerman PR, Stenmark KR, Fisher JH. Alpha‐skeletal actin messenger RNA increases in acute right ventricular hypertrophy. Am J Physiol 258: L173–L178, 1990.
 14. Bar H, Kreuzer J, Cojoc A, Jahn L. Upregulation of embryonic transcription factors in right ventricular hypertrophy. Basic Res Cardiol 98: 285‐294, 2003.
 15. Barger PM, Brandt JM, Leone TC, Weinheimer CJ, Kelly DP. Deactivation of peroxisome proliferator‐activated receptor‐alpha during cardiac hypertrophic growth. J Clin Invest 105: 1723‐1730, 2000.
 16. Basso C, Corrado D, Marcus FI, Nava A, Thiene G. Arrhythmogenic right ventricular cardiomyopathy. Lancet 373: 1289‐1300, 2009.
 17. Basso C, Thiene G, Corrado D, Angelini A, Nava A, Valente M. Arrhythmogenic right ventricular cardiomyopathy. Dysplasia, dystrophy, or myocarditis? Circulation 94: 983‐991, 1996.
 18. Belaguli NS, Sepulveda JL, Nigam V, Charron F, Nemer M, Schwartz RJ. Cardiac tissue enriched factors serum response factor and GATA‐4 are mutual coregulators. Mol Cell Biol 20: 7550‐7558, 2000.
 19. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal‐Ginard B, Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114: 763‐776, 2003.
 20. Bingham AJ, Ooi L, Kozera L, White E, Wood IC. The repressor element 1‐silencing transcription factor regulates heart‐specific gene expression using multiple chromatin‐modifying complexes. Mol Cell Biol 27: 4082‐4092, 2007.
 21. Bogaard HJ, Abe K, Vonk NA, Voelkel NF. The right ventricle under pressure: Cellular and molecular mechanisms of right‐heart failure in pulmonary hypertension. Chest 135: 794‐804, 2009.
 22. Bogaard HJ, Natarajan R, Henderson SC, Long CS, Kraskauskas D, Smithson L, Ockaili R, McCord JM, Voelkel NF. Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation 120: 1951‐1960, 2009.
 23. Bogaard HJ, Natarajan R, Mizuno S, Abbate A, Chau VQ, Hoke NN, Kraskauskas D, Salloum F, Voelkel NF. Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med 182: 652‐660, 2010.
 24. Bogaard JH, Noordegraaf NA, Voelkel NF. Right‐sided heart failure in chronic lung diseases and pulmonary arterial hypertension. In: Crawford MH, DiMarco JP, Paulus WJ, editors. Cardiology (3rd ed). Philadelphia: Elsevier, 2009, pp. 1159‐1169.
 25. Braun MU, Szalai P, Strasser RH, Borst MM. Right ventricular hypertrophy and apoptosis after pulmonary artery banding: Regulation of PKC isozymes. Cardiovasc Res 59: 658‐667, 2003.
 26. Bristow MR, Minobe W, Rasmussen R, Larrabee P, Skerl L, Klein JW, Anderson FL, Murray J, Mestroni L, Karwande SV. Beta‐adrengergic neuroeffector abnormalities in the failing human heart are produced by local rather than systemic mechanisms. J Clin Invest 89: 803‐815, 1992.
 27. Bristow MR, Zisman LS, Lowes BD, Abraham WT, Badesch DB, Groves BM, Voelkel NF, Lynch DM, Quaife RA. The pressure‐overloaded right ventricle in pulmonary hypertension. Chest 114: 101S‐106S, 1998.
 28. Bruneau BG. The developmental genetics of congenital heart disease. Nature 451: 943‐948, 2008.
 29. Buckingham M, Meilhac S, Zaffran S. Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet 6: 826‐835, 2005.
 30. Buermans HP, Redout EM, Schiel AE, Musters RJ, Zuidwijk M, Eijk PP, van Hardeveld C, Kasanmoentalib S, Visser FC, Ylstra B, and Warner S. Microarray analysis reveals pivotal divergent mRNA expression profiles early in the development of either compensated ventricular hypertrophy or heart failure. Physiol Genomics 21: 314‐323, 2005.
 31. Campbell SE, Korecky B, Rakusan K. Remodeling of myocyte dimensions in hypertrophic and atrophic rat hearts. Circ Res 68: 984‐996, 1991.
 32. Champion HC, Michelakis ED, Hassoun PM. Comprehensive invasive and noninvasive approach to the right ventricle‐pulmonary circulation unit: State of the art and clinical and research implication. Circuation 120: 992‐1007, 2009.
 33. Chaponnier C, Gabbiani G. Pathological situations characterized by altered actin isoform expression. J Pathol 204: 386‐395, 2004.
 34. Chen JX, Stinnet A. Ang‐1 gene therapy inhibits hypoxia‐inducible factor‐1alpha (HIF‐1alpha)‐prolyl‐4‐hydroxylase‐2, stabilizes HIF‐1alpha expression, and normalizes immature vasculature in db/db mice. Diabetes 57: 3335‐43, 2008.
 35. Chen Y, Hou M, Li Y, Traverse JH, Zhang P, Salvemini D, Fukai T, Bache RJ. Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart. Am J Physiol Heart Circ Physiol 288: H133–H141, 2005.
 36. Chen YF, Feng JA, Li P, Xing D, Ambalavanan N, Oparil S. Atrial natriuretic peptide‐dependent modulation of hypoxia‐induced pulmonary vascular remodeling. Life Sci 79: 1357‐1365, 2006.
 37. Chin KM, Kim NH, Rubin LJ. The right ventricle in pulmonary hypertension. Coron Artery Dis 16: 13‐18, 2005.
 38. Christoffersen TE, Aplin M, Strom CC, Sheikh SP, Skott O, Bush PK, Haunso S, Nielen LB. Increased natriuretic peptide receptor A and C gene expression in rats with pressure‐overload cardiac hypertrophy. Am J Physiol Heart Circ Physiol 290: H1635–H1641, 2006.
 39. D'Alonzo GE, Barst RJ, Ayres SM. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 115: 343‐349, 1991.
 40. Davidson C, Bonow R. Cardiac catheterization. In: Zipes D, Libby P, Bonow R, Braunwald E, editors. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine (7th ed). Philadelphia: Elsevier, 2005, p. 351‐362.
 41. De Groote P, Millaire A, Foucher‐Hossein C, Nugue O, Marchanidise X, Ducloux G, Lablanche JM. Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure. J Am Coll Cardiol 32: 948‐954, 1998.
 42. De Keulenaer, GW, Brutsaert DL. Systolic and diastolic heart failure: Different phenotypes of the same disease? Eur J Heart Fail 9: 136‐143, 2007.
 43. Dell'Italia LJ. The right ventricle: Anatomy, physiology, and clinical importance. Curr Probl Cardiol 16: 653‐720, 1991.
 44. Dell'Italia LJ, Walsh RA. Application of a time varying elastance model to right ventricular performance in man. Cardiovasc Res 22: 864‐874, 1988.
 45. Denault AY, Chaput M, Couture P, Hebert Y, Haddad F, Tardif JC. Dynamic right ventricular outflow tract obstruction in cardiac surgery. J Thorac Cardiovasc Surg 132: 43‐49, 2006.
 46. Deng Z, Morse JH, Stager 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: 737‐744, 2000.
 47. Diffee GM, Seversen EA, Stein TD, Johnson JA. Microarray expression analysis of effects of exercise training: Increase in atrial MLC‐1 in rat ventricles. Am J Physiol Heart Circ Physiol 284: H830–H837, 2003.
 48. Dorn GW, Force T. Protein kinase cascades in the regulation of cardiac hypertrophy. J Clin Invest 115: 527‐537, 2005.
 49. Dorn GW, Robbins J, Sugden PH. Phenotyping hypertrophy: Eschew obfuscation. Circ Res 92: 1171‐1175, 2003.
 50. Dorn GW. The fuzzy logic of physiological cardiac hypertrophy. Hypertension 49: 962‐970, 2007.
 51. Dupays L, Kotecha S, Mohun TJ. Tbx2 misexpression impairs deployment of second heart field derived progenitor cells to the arterial pole of the embryonic heart. Dev Biol 333: 121‐31, 2009.
 52. Elesgaray R, Caniffi C, Ierace DR, Jaime MF, Fellet A, Arranz C, Costa MA. Signaling cascade that mediates endothelial nitrate oxide synthase activation induced by atrial natriuretic peptide. Regul Pept 151: 130‐134, 2008.
 53. Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HH, Stasch JP. NO‐independent stimulators and activators of soluble guanylate cyclase: Discovery and therapeutic potential. Nat Rev Drug Discov 5: 755‐768, 2006.
 54. Eyries M, Siegfried G, Ciumas M, Montagne K, Agrapart M, Lebrin F, Soubrier F. Hypoxia‐induced apelin expression regulates endothelial cell proliferation and regenerative angiogenesis. Circ Res 103: 432‐440, 2008.
 55. Faber MJ, Dalinghaus M, Lankhuizen IM, Bezstarosti K, Verhoeven AJ, Duncker DJ, Helbinga WA, Lamers JMJ. Time dependent changes in cytoplasmic proteins of the right ventricle during prolonged pressure overload. J Mol Cell Cardiol 43: 197‐209, 2007.
 56. Falcao‐Pires I, Goncalves N, Henriques‐Coelho T, Moreira‐Goncalves D, Roncon‐Albuquerque R, Jr., Leite‐Moreira AF. Apelin decreases myocardial injury and improves right ventricular function in monocrotaline‐induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 296: H2007–H2014, 2009.
 57. Farb A, Burke AP, Virmani R. Anatomy and pathology of the right ventricle (including acquired tricuspid and pulmonic valve disease). Cardiol Clin 10: 1‐21, 1992.
 58. Friehs, I., Barillas R, Vasilyev NV, Roy N, McGowan FX, del Nido PJ. Vascular endothelial growth factor prevents apoptosis and preserves contractile function in hypertrophied infant heart. Circulation 114: 1290‐1295, 2006.
 59. Gaasch WH, Cole JS, Quinones MA, Alexander JK. Dynamic determinants of left ventricular diastolic pressure‐volume relations in man. Circulation 51: 317‐323, 1975.
 60. Ganong MD, William F Review of Medical Physiology. (22nd ed). The McGraw‐Hill Companies, Inc., 2005, p 587.
 61. Garry DJ, Olson EN. A common progenitor at the heart of development. Cell 127: 1101‐1104, 2006.
 62. Gatzoulis MA, Clark AL, Cullen S, Newman CG, Redington AN. Right ventricular diastolic function 15 to 35 years after repair of tetralogy of Fallot. Restrictive physiology predicts superior exercise performance. Circulation 91: 1775‐1781, 1995.
 63. Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse‐Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze‐Bahr E, Thierfelder L. Mutations in the desmosomal protein plakophilin‐2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet 36: 1162‐1164, 2004.
 64. Ghio, S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, Arbustini E, Recusani F, Tavazzi L. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 37; 183‐188, 2001.
 65. Gill, RM, Jones BD, Corbly AK, Wang J, Braz JC, Sandusky GE, Wang J, Shen W. Cardiac diastolic dysfunction in conscious dogs with heart failure induced by chronic coronary microembolization. Am J Physiol Heart Circ Physiol 291: H3154–H3158, 2006.
 66. Glenn DJ, Rahmutula D, Nishimoto M, Liang F, Gardner DG. Atrial natriuretic peptide suppresses endothelin gene expression and proliferation in cardiac fibroblasts through a GATA4‐dependent mechanism. Cardiovasc Res 84: 209‐217, 2009.
 67. Globits S, Burghuber OC, Koller J, Schenk P, Frank H, Grimm M, End A, Glogar D, Imhof H, Klepetko W. Effect of lung transplantation on right and left ventricular volumes and function measured by magnetic resonance imaging. Am J Respir Crit Care Med 149: 1000‐1004, 1994.
 68. Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right ventricular function in cardiovascular disease, part I: Anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation 117: 1436‐1448, 2008.
 69. Hardt SE, Sadoshima J. Negative regulators of cardiac hypertrophy. Cardiovasc Res 63: 500‐509, 2004.
 70. Harrison RE, Flanagan JA, Sankelo M, Abdalla SA, Rowell J, Machado RD, Elliott CG, Robbins IM, Olschewski H, McLaughlin V, Gruenig E, Karmeen 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: 865‐871, 2003.
 71. Harvey RP, Meilhac SM, Buckingham ME. Landmarks and lineages in the developing heart. Circ Res 104: 1235‐1237, 2009.
 72. Heerdt PM, Pleimann BE. The dose‐dependent effects of halothane on right ventricular contraction pattern and regional inotropy in swine. Anesth Analg 82: 1152‐1158, 1996.
 73. Hein S, Arnon E, Kostin S, Schonburg M, Elsasser A, Polyakova V, Bauer EP, Klövekorn WP, Schaper J. Progression from compensated hypertrophy to failure in the pressure‐overloaded human heart: Structural deterioration and compensatory mechanisms. Circulation 107: 984‐991, 2003.
 74. Heineke J, Auger‐Messier M, Xu J, Oka T, Sargent MA, York A, Klevitsky R, Vaikunth S, Duncan SA, Aronow BJ, Robbins J, Crombleholme TM, Molkentin JD. Cardiomyocyte GATA4 functions as a stress‐responsive regulator of angiogenesis in the murine heart. J Clin Invest 117: 3198‐3210, 2007.
 75. Herron TJ, McDonald KS. Small amounts of alpha‐myosin heavy chain isoform expression significantly increase power output of rat cardiac myocyte fragments. Circ Res 90: 1150‐1152, 2002.
 76. Hill JA, Olson EN. Cardiac plasticity. N Engl J Med 358: 1370‐1380, 2008.
 77. Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R, Komuro I. Tbx5 associates with Nkx2‐5 and synergistically promotes cardiomyocyte differentiation. Nat Genet 28: 276‐280, 2001.
 78. Ho SY, Nihoyannopoulos P. Anatomy, echocardiography, and normal right ventricular dimensions. Heart 92 Suppl 1: i2‐i13, 2006.
 79. Hoper MM, Voelkel NF, Bates TO, Allard JD, Horan M, Shepherd D, Tuder RM. Prostaglandins induce vascular endothelial growth factor in a human monocytic cell line and rat lungs via cAMP. Am J Respir Cell Mol Biol 17: 748‐756, 1997.
 80. Houweling AC, van Borren MM, Moorman AF, Christoffels VM. Expression and regulation of the atrial natriuretic factor encoding gene Nppa during development and disease. Cardiovasc Res 67: 583‐593, 2005.
 81. Hu H, Sachs F. Stretch‐activated ion channels in the heart. J Mol Cell Cardiol 29: 1511‐1523, 1997.
 82. Iwanaga Y, Kihara Y, Takenaka H, Kita T. Down‐regulation of cardiac apelin system in hypertrophied and failing hearts: Possible role of angiotensin II‐angiotensin type 1 receptor system. J Mol Cell Cardiol 41: 798‐806, 2006.
 83. Jamshidi Y, Montgomery HE, Hense HW, Myerson SG, Torra IP, Staels B, World MJ, Doering A, Erdmann J, Hengstenberg C, Humphries SE, Schunkert H, Flavell DM. Peroxisome proliferator‐activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension. Circulation 105: 950‐955, 2002.
 84. Jiang L. Right Ventricle. In: Weyman AE, editor. Principle and Practice of Echocardiography. Baltimore: Lippincott Williams & Wilkins; 1994, p. 901‐921.
 85. Kass, D.A., Bronzwaer JG, Paulus WJ. What Mechanisms Underlie Diastolic Dysfunction in Heart Failure? Circ Res 94: 1533‐1542, 2004.
 86. Katsumi A, Orr AW, Tzima E, Schwartz MA. Integrins in mechanotransduction. J Biol Chem 279: 12001‐12004, 2004.
 87. Kattman SJ, Huber TL, Keller GM. Multipotent flk‐1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Dev Cell 11: 723‐732, 2006.
 88. Kawut SM, Al‐Naamani N, Agerstrand C, Rosenweig EB, Rowan C, Barst RJ, Bergmann S, Horn EH. Determinants of right ventricular ejection fraction in pulmonary arterial hypertension. Chest 135 (3): 752‐759, 2009.
 89. Kidoya H, Ueno M, Yamada Y, Mochizuki N, Nakata M, Yano T, Fujii R, Takakura N. Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis. EMBO J 27: 522‐534, 2008.
 90. Kim SZ, Cho KW, Kim SH. Modulation of endocardial natriuretic peptide receptors in right ventricular hypertrophy. Am J Physiol 277: H2280–H2289, 1999.
 91. Kinch JW, Ryan TJ. Right ventricular infarction. N Engl J Med 330: 1211‐1217, 1994.
 92. Kiserus T, Archarya G. The fetal circulation. Prenat Diagn 24: 1049‐1059, 2004.
 93. Klinger JR, Warburton RR, Pietras LA, Smithies O, Swift R, Hill NS. Genetic disruption of atrial natriuretic peptide causes pulmonary hypertension in normoxic and hypoxic mice. Am J Physiol 276: L868–L874, 1999.
 94. Klionsky DJ, Emr SD. Authophagy as a regulated pathway of cellular degradation. Science 290: 1717‐1721, 2000.
 95. Kuba K, Zhang L, Imai Y, Arab S, Chen M, Maekawa Y, Leschnik M, Leibbrandt A, Markovic M, Schwaighofer J, Beetz N, Musialek R, Neely GG, Komnenovic V, Kolm U, Metzler B, Ricci R, Hara H, Meixner A, Nghiem M, Chen X, Dawood F, Wong KM, Sarao R, Cukerman E, Kimura A, Hein L, Thalhammer J, Liu PP, Penninger JM. Impaired heart contractility in apelin gene‐deficient mice associated with aging and pressure overload. Circ Res 101: e32–e42, 2007.
 96. Lafontan M, Moro C, Berlan M, Crampes F, Sengenes C, Galitzky J. Control of lipolysis by natriuretic peptides and cyclic GMP. Trends Endocrinol Metab 19: 130‐137, 2008.
 97. Lakshminrusimha S, D'Angelis CA, Russell JA, Nielsen LC, Gugino SF, Nickerson PA, Steinhorn RH. C‐type natriuretic peptide system in fetal ovine pulmonary vasculature. Am J Physiol Lung Cell Mol Physiol 281: L361–L368, 2001.
 98. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Philips JA, Loyd JE, Nichols WC, Trembath RC. Heterozygous germ‐like mutations in BMPR2, encoding a TGF‐beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet 26: 81‐84, 2000.
 99. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ. Recommendations for chamber quantification: A report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18: 1440‐1463, 2005.
 100. Lee, S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, Ferrara N, Nagy A, Roos KP, Iruela‐Arispe ML. Autocrine VEGF signaling is required for vascular homeostasis. Cell 130 (4): 691‐703, 2007.
 101. Lee Y, Shioi T, Kasahara H, Jobe SM, Wiese RJ, Markham BE, Izumo S. The cardiac tissue‐restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression. Mol Cell Biol 18: 3120‐3129, 1998.
 102. Leeuwenburgh BP, Helbing WA, Wenink AC, Steendijk P, de JR, Dreef EJ, Gittenberger‐de Groot AC, Baan J, van der Laarse A. Chronic right ventricular pressure overload results in a hyperplastic rather than a hypertrophic myocardial response. J Anat 212: 286‐294, 2008.
 103. Lei B, Jaing X, Martin‐Puig S, Caron L, Zhu S, Shao Y, Roberts DJ, Huang PL, Domian IJ, Chien KR. Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature 460: 113‐117, 2009.
 104. Leyton RA, Sonnenblick EH. The sarcomere as the basis of Starling's law of the heart in the left and right ventricles. Methods Achiev Exp Pathol 5: 22‐59, 1971.
 105. Li XM, Ma YT, Yang YN, Liu F, Chen BD, Han W, Zhang JF, Xiao G. Downregulation of survival signaling pathways and increased apoptosis in the transition of pressure overload‐induced cardiac Hypertrophy towards to heart failure. Clin Exp Pharmacol Physiol 36: 1054‐1061, 2009.
 106. Lin Q, Schwarz J, Bucana C, Olson EN. Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science 276: 1404‐1407, 1997.
 107. Lorenz CH, Walker ES, Morgan VL, Klein SS, Graham TP, Jr. Normal human right and left ventricular mass, systolic function, and gender differences by cine magnetic resonance imaging. J Cardiovasc Magn Reson 1: 7‐21, 1999.
 108. Louzier V, Eddahibi S, Raffestin B, Deprez I, Adam M, Levame M, Eloit M, Adnot S. Adenovirus‐mediated atrial natriuretic protein expression in the lung protects rats from hypoxia‐induced pulmonary hypertension. Hum Gene Ther 12: 503‐513, 2001.
 109. Lowes BD, Minobe W, Abraham WT, Rizeq MN, Bohlmeyer TJ, Quaife RA, Roden RL, Dutcher DL, Robertson AD, Voelkel NF, Badesch DB, Groves BM, Gilbert EM, Bristow MR. Changes in gene expression in the intact human heart. Downregulation of alpha‐myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest 100: 2315‐2324, 1997.
 110. MacKenna DA, Dolfi F, Vuori K, Ruoslahti E. Extracellular signal‐regulated kinase and c‐Jun NH2‐terminal kinase activation by mechanical stretch is integrin‐dependent and matrix‐specific in rat cardiac fibroblasts. J Clin Invest 101: 301‐310, 1998.
 111. MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease, Part 1. Am J Respir Crit Care Med 150: 833‐852, 1994.
 112. Maeda K, Tsutamoto T, Wada A, Hisanaga T, Nishimura T, Yamada H, Sasaki Y, Kinoshita M. Low dose synthetic human atrial natriuretic peptide infusion in a patient with mitral stenosis and severe pulmonary hypertension. Jpn Circ J 63: 816‐818, 1999.
 113. Mann DL. Basic mechanisms of left ventricular remodeling: The contribution of wall stress. J Card Fail 10: S202–S206, 2004.
 114. Mao S, Budoff MJ, Oudiz RJ, Bakhsheshi H, Wang S, Brundage BH. Effect of exercise on left and right ventricular ejection fraction and wall motion. Int J Cardiol 71: 23‐31, 1999.
 115. Markel TA, Wairiuko GM, Lahm T, Crisostomo PR, Wang M, Herring CM et al. The right heart and its distinct mechanisms of development, function, and failure. J Surg Res 146: 304‐313, 2008.
 116. McClure LE, Peacock AJ. Cardiac magnetic resonance imaging for the assessment of the heart and pulmonary circulation in pulmonary hypertension. Eur Respir J 33: 1454‐66, 2009.
 117. McFadden DG, Barbosa AC, Richardson JA, Schneider MD, Srivastava D, Olson EN. The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage‐dependent manner. Development 132: 189‐201, 2005.
 118. Miura T, Miki T. GSK‐3beta, a therapeutic target for cardiomyocyte protection. Circ J 73: 1184‐1192, 2009.
 119. Miyata S, Minobe W, Bristow MR, Leinwand LA. Myosin heavy chain isoform expression in the failing and nonfailing human heart. Circ Res 86: 386‐390, 2000.
 120. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self‐digestion. Nature 451: 1069‐1075, 2008.
 121. Molkentin JD, Dorn GW. Cytoplasmic signaling pathways that regulate cardiac hypertrophy. Annu Rev Physiol 63: 391‐426, 2001.
 122. Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y. Multipotent embryonic isl1 +progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127: 1151‐1165, 2006.
 123. Mori T, Chen YF, Feng JA, Hayashi T, Oparil S, Perry GJ. Volume overload results in exaggerated cardiac hypertrophy in the atrial natriuretic peptide knockout mouse. Cardiovasc Res 61: 771‐779, 2004.
 124. Morisco C, Sadoshima J, Trimarco B, Arora R, Vatner DE, Vatner SF. Is treating cardiac hypertrophy salutary or detrimental: The two faces of Janus. Am J Physiol Heart Circ Physiol 284: H1043–H1047, 2003.
 125. Mudd JO, Kass DA. Tackling heart failure in the twenty‐first century. Nature 451: 919‐928, 2008.
 126. Nakajima K, Onishi K, Dohi K, Tanabe M, Kurita T, Yamanaka T, Ito M, Isaka N, Norbori T, Nakano T. Effects of human atrial natriuretic peptide on cardiac function and hemodynamics in patients with high plasma BNP levels. Int J Cardiol 104: 332‐337, 2005.
 127. Nana‐Sinkam SP, Lee JD, Sotto‐Santiago S, Stearman RS, Keith RL, Choudhury Q, Cool C, Parr J, Moore MD, Bull TM, Voelkel NF, Geraci MW. Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke. Am J Respir Crit Care Med. 175: 676‐85, 2007.
 128. Oka M, Homma N, McMurtry IF. Rho kinase‐mediated vasoconstriction in rat models of pulmonary hypertension. Methods Enzymol 439: 191‐204, 2008.
 129. Olson EN. A decade of discoveries in cardiac biology. Nat Med 10: 467‐474, 2004.
 130. Olson EN. Gene regulatory networks in the evolution and development of the heart. Science 313: 1922‐1927, 2006
 131. Orlic D, Kajstura J, Chimenti S, Bodine DM, Leri A, Anversa P. Bone marrow stem cells regenerate infarcted myocardium. Pediatr Transplant 7: 86‐88, 2003.
 132. Owan, TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355: 251‐259, 2006.
 133. Patrizio M, Vago V, Musumeci M, Fecchi K, Sposi NM, Mattei E, Catalanod L, Statia T, Giuseppe M. cAMP‐mediated beta‐adrenergic signaling negatively regulates Gq‐coupled receptor‐mediated fetal gene response in cardiomyocytes. J Mol Cell Cardiol 45: 761‐769, 2008.
 134. Phan D, Rasmussen TL, Nakagawa O, McAnally J, Gottlieb PD, Tucker PW, Richardson JA, Bassel‐Duby R, Olson EN. BOP, a regulator of right ventricular heart development, is a direct transcriptional target of MEF2C in the developing heart. Development 132: 2669‐2678, 2005.
 135. Pilichou K, Remme CA, Basso C, Campian ME, Rizzo S, Barnett P, Scicluna BP, Bauce B, van den Hoff MJ, de Bakker JM, Tan HL, Valente M, Nava A, Wilde AA, Moorman AF, Thiene G, Bezzina CR. Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2‐related arrhythmogenic right ventricular cardiomyopathy. J Exp Med 206: 1787‐1802, 2009.
 136. Plageman TF Jr, Yutzey KE. Microarray analysis of Tbx5‐induced genes expressed in the developing heart. Dev Dyn 235: 2868‐2880, 2006.
 137. Polak JF, Holman BL, Wynne J, Colucci WS. Right ventricular ejection fraction: An indicator of increased mortality in patients with congestive heart failure associated with coronary artery disease. J Am Coll Cardiol 37: 183‐188, 2001.
 138. Prall OW, Menon MK, Solloway MJ, Watanabe Y, Zaffran S, Bajolle F, Biben C, McBride JJ, Robertson BR, Chaulet H, Stennard FA, Wise N, Schaft D, Wolstein O, Furtado MB, Shiratori H, Chien KR, Hamada H, Black BL, Saga Y, Robertson EJ, Buckingham ME, Harvey RP. An Nkx2‐5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell 128: 947‐959, 2007.
 139. Quaife RA, Chen MY, Lynch D, Badesch DB, Groves BM, Wolfel E, Robertson AD, Bristow MR, Voelkel NF. Importance of right ventricular end‐systolic regional wall stress in idiopathic pulmonary arterial hypertension: A new method for estimation of right ventricular wall stress. Eur J Med Res 11: 214‐220, 2006.
 140. Quartermain MD, Cohen MS, Dominguez TE, Tian Z, Donaghue DD. Left ventricle to right ventricle size discrepancy in the fetus: The presence of critical congenital disease can be reliably predicted. J Am Soc Echocardio 22: 1296‐301, 2009.
 141. Ross RS, Pham C, Shai SY, Goldhaber JI, Fenczik C, Glembotski CC, Robertson AD, Bristow MR, Voelkel NF. Beta1 integrins participate in the hypertrophic response of rat ventricular myocytes. Circ Res 82: 1160‐1172, 1998.
 142. Rudolph AM. Myocardial growth before and after birth: Clinical implications. Acta Paediatr 89: 129‐33, 2000.
 143. Ryan US. Endothelial cell activation response in lung biology in health disease. In: Ryan US, Dekker M, editors Vol. 32. New York: Basel, 1987, p. 3‐33.
 144. Sheikh AM, Barrett C, Villamizar N, Alzate O, Valente AM, Herlong JR, Craig D, Lodge A, Lawson J, Milano C, Jaggers J. Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model. J Thorac Cardiovasc Surg 137: 1146‐1153, 2009.
 145. Spees JL, Whitney MJ, Sullivan DE, Lasky JA, Laboy M, Ylostalo J. Bone marrow progenitor cells contribute to repair and remodeling of the lung and heart in a rat model of progressive pulmonary hypertension. FASEB J 22: 1226‐1236, 2008.
 146. Srivastava D. Making or breaking the heart: From lineage determination to morphogenesis. Cell 126: 1037‐1048, 2006.
 147. Starling MR, Walsh RA, Dell'Italia LJ, Mancini GB, Lasher JC, Lancaster JL. The relationship of various measures of end‐systole to left ventricular maximum time‐varying elastance in man. Circulation 76: 32‐43, 1987.
 148. Szokodi I, Tavi P, Foldes G, Voutilainen‐Myllyla S, Ilves M, Tokola H, Pikkarainen S, Piuhola J, Rysä J, Tóth M, Ruskoaho H. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res 91: 434‐440, 2002.
 149. Taraseviciene‐Stewart L, Kasahara Y, Alger L, Hirth P, Mc MG, Waltenberger J, Voelkel NF, Tudor 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: 427‐438, 2001.
 150. Taraseviciene‐Stewart L, Scerbavicius R, Choe KH, Cool C, Wood K, Tuder RM, Burns N, Kasper M, Voelkel NF. Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 291: L668–L676, 2006.
 151. Usui S, Yao A, Hatano M, Kohmoto O, Takahashi T, Nagai R, Kinugawa K. Upregulated neurohormonal factors are associated with left ventricular remodeling and poor prognosis in rats with monocrotaline‐induced pulmonary arterial hypertension. Circ J 70: 1208‐1215, 2006.
 152. Van Straten A, Vliegen HW, Hazekamp MG, de RA. Right ventricular function late after total repair of tetralogy of Fallot. Eur Radiol 15: 702‐707, 2005.
 153. VanBuren P, Okada Y. Thin filament remodeling in failing myocardium. Heart Fail Rev 10: 199‐209, 2005.
 154. Vasan RS, Benjamin EJ. Diastolic Heart failure—no time to relax. N Engl J Med 344: 56‐59, 2001.
 155. Vikstrom KL, Bohlmeyer T, Factor SM, Leinwand LA. Hypertrophy, pathology, and molecular markers of cardiac pathogenesis. Circ Res 82: 773‐778, 1998.
 156. Voelkel NF, Tudor RM. Right ventricular function and failure: Report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 114 (17): 1883‐1891, 2006.
 157. Vornehm ND, Wang M, Abarbanell A, Herrmann J, Well B, Tan J, Wang Y, Kelly M, Meldrum DR. Acute postischemic treatment with estrogen receptor‐alpha agonist or estrogen receptor‐beta agonist improves myocardial recovery. Surgery 146: 145‐154, 2009.
 158. Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN. Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. Cell 105: 851‐862, 2001.
 159. Weiss RG, Gerstenblith G, Bottomley PA. ATP flux through creatine kinase in the normal, stressed, and failing human heart. Proc Natl Acad Sci U S A 102: 808‐813, 2005.
 160. Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL, Schultheiss TM, Orkin SH. Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell 127: 1137‐1150, 2006.
 161. Yamagishi H, Yamagishi C, Nakagawa O, Harvey RP, Olson EN, Srivastava D. The combinatorial activities of Nkx2.5 and dHAND are essential for cardiac ventricle formation. Dev Biol 239: 190‐203, 2001.
 162. Yamamoto K, Ohki R, Lee RT, Ikeda U, Shimada K. Peroxisome proliferator‐activated receptor gamma activators inhibit cardiac hypertrophy in cardiac myocytes. Circulation 104: 1670‐1675, 2001.
 163. Yet SF, Perrella MA, Layne MD, Hsieh CM, Maemura K, Kobzik L, Wiesel P, Christou H, Kourembanas S, Lee ME. Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase‐1 null mice. J Clin Invest 103: R23–R29, 1999.
 164. Zeisberg EM, Ma Q, Juraszek AL, Moses K, Schwartz RJ, Izumo S, Wiesel P, Christou H, Kourembanas S, Lee ME. Morphogenesis of the right ventricle requires myocardial expression of Gata4. J Clin Invest 115: 1522‐1531, 2005.
 165. Zeisberg E, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, Neilson EG, Sayegh MH, Izumo S, Kalluri R. Endothelial‐to‐Mesenchymal Transition Contributes to Cardiac Fibrosis. Nat Med 13: 952‐961, 2007.
 166. Zhao Y, Ransom JF, Li A, Vedantham V, von DM, Muth AN et al. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA‐1‐2. Cell 129: 303‐317, 2007.
 167. Zierer A, Voeller RK, Melby SJ, Steendijk P, Moon MR. Impact of calcium‐channel blockers on right heart function in a controlled model of chronic pulmonary hypertension. Eur J Anaesthesiol 26: 253‐259, 2009.
 168. Zisman LS, Asano K, Dutcher DL, Ferdensi A, Robertson AD, Jenkin M, Bush EW, Bohlmeyer T, Perryman MG, Bristow MR. Differential regulation of cardiac angiotensin converting enzyme binding sites and AT1 receptor density in the failing human heart. Circulation 98: 1735‐1741, 1998.

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Norbert F. Voelkel, Ramesh Natarajan, Jennifer I. Drake, Herman J. Bogaard. Right Ventricle in Pulmonary Hypertension. Compr Physiol 2011, 1: 525-540. doi: 10.1002/cphy.c090008