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Receptor-Signaling Pathways in Heart Failure

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Principles of Molecular Cardiology

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Heart failure, a progressive disorder characterized by deterioration of cardiac function and premature myocardial cell death, results from several common heart diseases such as coronary atherosclerosis, hypertension, and valvular diseases (1,2). With almost 550,000 new cases diagnosed each year, heart failure affects an estimated 4.7 million Americans, and costs associated with the disease range from $10 billion to $40 billion per year (3). The aggregate 5-year mortality of patients with heart failure is about 50%, while the 1-year mortality of patients with advanced disease may exceed 50% (3). To maintain adequate myocardial contractility in response to injury, the heart uses several mechanisms, including hypertrophy of myocardial cells, changing the energetics of myocardial cell contraction, and upregulating transcription of several genes (4,5).

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References

  1. Katz AM, Lorell BH. Regulation of cardiac contraction and relaxation. Circulation 2000;102:IV69–IV74.

    PubMed  CAS  Google Scholar 

  2. Towbin JA, Bowles NE. The failing heart. Nature 2002;415: 227–233.

    Article  PubMed  CAS  Google Scholar 

  3. 2001 Heart and Stroke Statistical Update. Dallas: American Heart Association. 2001.

    Google Scholar 

  4. Alpert NR, Mulieri LA. Increased myothermal economy of isometric force generation in compensated cardiac hypertrophy induced by pulmonary artery constriction in the rabbit. A characterization of heat liberation in normal and hypertrophied right ventricular papillary muscles. Circ Res 1982;50:491–500.

    PubMed  CAS  Google Scholar 

  5. Chien KR. Genomic circuits and the integrative biology of cardiac diseases. Nature 2000;407:227–232.

    Article  PubMed  CAS  Google Scholar 

  6. MacLellan WR, Schneider MD. Genetic dissection of cardiac growth control pathways. Annu Rev Physiol 2000;62:289–319.

    Article  PubMed  CAS  Google Scholar 

  7. Molkentin JD. Calcineurin and beyond: cardiac hypertrophic signaling. Circ Res 2000;87:731–738.

    PubMed  CAS  Google Scholar 

  8. Sadoshima J, Izumo S. The cellular and molecular response of cardiac myocytes to mechanical stress. Annu Rev Physiol 1997;59:551–571.

    Article  PubMed  CAS  Google Scholar 

  9. Molkentin JD, Dorn IG II. Cytoplasmic signaling pathways that regulate cardiac hypertrophy. Annu Rev Physiol 2001;63:391–426.

    Article  PubMed  CAS  Google Scholar 

  10. Gwathmey JK, Copelas L, MacKinnon R, et al. Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 1987;61:70–76.

    PubMed  CAS  Google Scholar 

  11. Tsutsui H, Ishihara K, Cooper GT. Cytoskeletal role in the contractile dysfunction of hypertrophied myocardium. Science 1993;260:682–687.

    Article  PubMed  CAS  Google Scholar 

  12. Urabe Y, Mann DL, Kent RL, et al. Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation. Circ Res 1992;70:131–147.

    PubMed  CAS  Google Scholar 

  13. Rockman HA, Koch WJ, Lefkowitz RJ. Seven-transmembrane-spanning receptors and heart function. Nature 2002;415:206–212.

    Article  PubMed  CAS  Google Scholar 

  14. Chien KR. Stress pathways and heart failure. Cell 1999;98:555–558.

    Article  PubMed  CAS  Google Scholar 

  15. Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 1975;56: 56–64.

    PubMed  CAS  Google Scholar 

  16. Osier W. The Principles and Practice of Medicine. New York: Appleton;1892.

    Google Scholar 

  17. Kannel WB, Castelli WP, McNamara PM, McKee PA, Feinleib M. Role of blood pressure in the development of congestive heart failure. The Framingham Study. N Engl J Med 1972;287:781–787.

    Article  PubMed  CAS  Google Scholar 

  18. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990;322:1561–1566.

    Article  PubMed  CAS  Google Scholar 

  19. Esposito G, Rapacciuolo A, Naga Prasad SV, et al. Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress. Circulation 2002; 105:85–92.

    Article  PubMed  CAS  Google Scholar 

  20. Hill JA, Karimi M, Kutschke W, et al. Cardiac hypertrophy is not a required compensatory response to short-term pressure overload. Circulation 2000;101:2863–2869.

    PubMed  CAS  Google Scholar 

  21. Gudermann T, Nurnberg B, Schultz G. Receptors and G proteins as primary components of transmembrane signal transduction. Part 1. G-protein-coupled receptors: structure and function. J Mol Med 1995;73:51–63.

    Article  PubMed  CAS  Google Scholar 

  22. Lefkowitz RJ. G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. J Biol Chem 1998;273:18677–18680.

    Article  PubMed  CAS  Google Scholar 

  23. Clapham DE, Neer EJ. G protein beta gamma subunits. Annu Rev Pharmacol Toxicol 1997;37:167–203.

    Article  PubMed  CAS  Google Scholar 

  24. Gutkind JS. The pathways connecting G protein-coupled receptors to the nucleus through divergent mitogen-activated protein kinase cascades. J Biol Chem 1998;273:1839–1842.

    Article  PubMed  CAS  Google Scholar 

  25. Kamp TJ, Hell JW. Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C. Circ Res 2000;87:1095–1102.

    PubMed  CAS  Google Scholar 

  26. Marx SO, Reiken S, Hisamatsu Y, et al. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryan-odine receptor): defective regulation in failing hearts. Cell 2000;101:365–376.

    Article  PubMed  CAS  Google Scholar 

  27. Tada M, Toyofuku T. SR Ca(2+)-ATPase/phospholamban in cardiomyocyte function. J Card Fail 1996;2:S77–S85.

    Article  PubMed  CAS  Google Scholar 

  28. Osaki J, Haneda T, Sakai H, Kikuchi K. cAMP-mediated c-fos expression in pressure-overloaded acceleration of protein synthesis in adult rat heart. Cardiovasc Res 1997;33:631–640.

    Article  PubMed  CAS  Google Scholar 

  29. Ferguson SS. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev 2001; 53:1–24.

    PubMed  CAS  Google Scholar 

  30. Sibley DR, Strasser RH, Benovic JL, Daniel K, Lefkowitz RJ. Phosphorylation/dephosphorylation of the beta-adrenergic receptor regulates its functional coupling to adenylate cyclase and subcellular distribution. Proc Natl Acad Sci USA 1986;83:9408–9412.

    Article  PubMed  CAS  Google Scholar 

  31. Yu SS, Lefkowitz RJ, Hausdorff WP. Beta-adrenergic receptor sequestration. A potential mechanism of receptor resensitization. J Biol Chem 1993;268:337–341.

    PubMed  CAS  Google Scholar 

  32. Luttrell LM, Roudabush FL, Choy EW, et al. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc Natl Acad Sci USA 2001;98:2449–2454.

    Article  PubMed  CAS  Google Scholar 

  33. McDonald PH, Chow CW, Miller WE, et al. Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 2000;290:1574–1577.

    Article  PubMed  CAS  Google Scholar 

  34. Koch WJ, Lefkowitz RJ, Rockman HA. Functional consequences of altering myocardial adrenergic receptor signaling. Annu Rev Physiol 2000;62:237–260.

    Article  PubMed  CAS  Google Scholar 

  35. Caron MG, Lefkowitz RJ. Catecholamine receptors: structure, function, and regulation. Recent Prog Horm Res 1993;48:277–290.

    PubMed  CAS  Google Scholar 

  36. Brodde OE. Beta-adrenoceptors in cardiac disease. Pharmacol Ther 1993;60:405–430.

    Article  PubMed  CAS  Google Scholar 

  37. Gauthier C, Leblais V, Kobzik L, et al. The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. J Clin Invest 1998;102:1377–1384.

    PubMed  CAS  Google Scholar 

  38. Gauthier C, Tavernier G, Charpentier F, Langin D, Le Marec H. Functional beta3-adrenoceptor in the human heart. J Clin Invest 1996;98:556–562.

    PubMed  CAS  Google Scholar 

  39. Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984;311:819–823.

    Article  PubMed  CAS  Google Scholar 

  40. Bristow MR. Why does the myocardium fail? Insights from basic science. Lancet 1998;352:8–14.

    Article  CAS  Google Scholar 

  41. Bristow MR, Ginsburg R, Minobe W, et al. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med 1982;307:205–211.

    Article  PubMed  CAS  Google Scholar 

  42. Bristow MR, Hershberger RE, Port JD, Minobe W, Rasmussen R. Beta 1-and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol 1989;35:295–303.

    PubMed  CAS  Google Scholar 

  43. Ungerer M, Bohm M, Elce JS, Erdmann E, Lohse MJ. Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart. Circulation 1993;87:454–463.

    PubMed  CAS  Google Scholar 

  44. Bristow MR, Minobe WA, Raynolds MV, et al. Reduced beta 1 receptor messenger RNA abundance in the failing human heart. J Clin Invest 1993;92:2737–2745.

    PubMed  CAS  Google Scholar 

  45. Lefkowitz RJ, Rockman HA, Koch WJ. Catecholamines, cardiac beta-adrenergic receptors, and heart failure. Circulation 2000;101:1634–1637.

    PubMed  CAS  Google Scholar 

  46. Engelhardt S, Hein L, Wiesmann F, Lohse MJ. Progressive hypertrophy and heart failure in betal-adrenergic receptor transgenic mice. Proc Natl Acad Sci USA 1999;96:7059–7064.

    Article  PubMed  CAS  Google Scholar 

  47. Liggett SB, Tepe NM, Lorenz JN, et al. Early and delayed consequences of beta(2)adrenergic receptor overexpression in mouse hearts: critical role for expression level. Circulation 2000;101:1707–1714.

    PubMed  CAS  Google Scholar 

  48. Milano CA, Allen LF, Rockman HA, et al. Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor. Science 1994;264:582–586.

    Article  PubMed  CAS  Google Scholar 

  49. Dorn GW II, Tepe NM, Lorenz JN, Koch WJ, Liggett SB. Low-and high-level transgenic expression of beta2-adrenergic receptors differentially affect cardiac hypertrophy and function in Galphaq-overexpressing mice. Proc Natl Acad Sci USA 1999;96:6400–6405.

    Article  PubMed  CAS  Google Scholar 

  50. Rohrer DK, Desai KH, Jasper JR, et al. Targeted disruption of the mouse betal-adrenergic receptor gene: developmental and cardiovascular effects. Proc Natl Acad Sci USA 1996;93:7375–7380.

    Article  PubMed  CAS  Google Scholar 

  51. Chruscinski AJ, Rohrer DK, Schauble E, Desai KH, Bernstein D, Kobilka BK. Targeted disruption of the beta2 adrenergic receptor gene. J Biol Chem 1999;274:16694–16700.

    Article  PubMed  CAS  Google Scholar 

  52. Xiao RP, Avdonin P, Zhou YY, et al. Coupling of beta2-adrenoceptor to Gi proteins and its physiological relevance in murine cardiac myocytes. Circ Res 1999;84:43–52.

    PubMed  CAS  Google Scholar 

  53. Zhu WZ, Zheng M, Koch WJ, Lefkowitz RJ, Kobilka BK, Xiao RP. Dual modulation of cell survival and cell death by beta(2)-adrenergic signaling in adult mouse cardiac myocytes. Proc Natl Acad Sci USA 2001;98:1607–1612.

    Article  PubMed  CAS  Google Scholar 

  54. Geng YJ, Ishikawa Y, Vatner DE, et al. Apoptosis of cardiac myocytes in Gsalpha transgenic mice. Circ Res 1999;84:34–42.

    PubMed  CAS  Google Scholar 

  55. Wollert KC, Drexler H. The renin-angiotensin system and experimental heart failure. Cardiovasc Res 1999;43:838–849.

    Article  PubMed  CAS  Google Scholar 

  56. Touyz RM, Schiffrin EL. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev 2000;52:639–672.

    PubMed  CAS  Google Scholar 

  57. Sugden PH, Clerk A. Regulation of the ERK subgroup of MAP kinase cascades through G protein-coupled receptors. Cell Signal 1997;9:337–351.

    Article  PubMed  CAS  Google Scholar 

  58. Sugden PH, Clerk A. Cellular mechanisms of cardiac hypertrophy. J Mol Med 1998;76:725–746.

    Article  PubMed  CAS  Google Scholar 

  59. Haendeler J, Berk BC. Angiotensin II mediated signal transduction. Important role of tyrosine kinases. Regul Pept 2000;95:1–7.

    Article  PubMed  CAS  Google Scholar 

  60. Griendling KK, Murphy TJ, Alexander RW. Molecular biology of the renin-angiotensin system. Circulation 1993;87:1816–1828.

    PubMed  CAS  Google Scholar 

  61. Rockman HA, Wachhorst SP, Mao L, Ross J Jr. ANG II receptor blockade prevents ventricular hypertrophy and ANF gene expression with pressure overload in mice. Am J Physiol 1994;266:H2468–H2475.

    PubMed  CAS  Google Scholar 

  62. Esther CR, Marino EM, Howard TE, et al. The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice. J Clin Invest 1997;99:2375–2385.

    PubMed  CAS  Google Scholar 

  63. Sadoshima J, Xu Y, Slayter HS, Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993;75:977–984.

    Article  PubMed  CAS  Google Scholar 

  64. Harada K, Komuro I, Shiojima I, et al. Pressure overload induces cardiac hypertrophy in angiotensin II type 1A receptor knockout mice. Circulation 1998;97:1952–1959.

    PubMed  CAS  Google Scholar 

  65. Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 2000;52:11–34.

    PubMed  CAS  Google Scholar 

  66. Kim S, Ohta K, Hamaguchi A, Yukimura T, Miura K, Iwao H. Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats. Hypertension 1995;25:1252–1259.

    PubMed  CAS  Google Scholar 

  67. Lijnen P, Petrov V. Antagonism of the renin-angiotensin system, hypertrophy and gene expression in cardiac myocytes. Methods Find Exp Clin Pharmacol 1999;21:363–374.

    Article  PubMed  CAS  Google Scholar 

  68. Lijnen P, Petrov V. Antagonism of the renin-angiotensin-aldosterone system and collagen metabolism in cardiac fibroblasts. Methods Find Exp Clin Pharmacol 1999;21:215–227.

    Article  PubMed  CAS  Google Scholar 

  69. Lorell BH. Role of angiotensin AT1, and AT2 receptors in cardiac hypertrophy and disease. Am J Cardiol 1999;83:48H–52H.

    Article  PubMed  CAS  Google Scholar 

  70. Kudoh S, Komuro I, Hiroi Y, et al. Mechanical stretch induces hypertrophic responses in cardiac myocytes of angiotensin II type la receptor knockout mice. J Biol Chem 1998;273:24037–24043.

    Article  PubMed  CAS  Google Scholar 

  71. Bartunek J, Weinberg EO, Tajima M, Rohrbach S, Lorell BH. Angiotensin II type 2 receptor blockade amplifies the early signals of cardiac growth response to angiotensin II in hypertrophied hearts. Circulation 1999 99:22–25.

    PubMed  CAS  Google Scholar 

  72. Lin F, Owens WA, Chen S, et al. Targeted alpha(1A)-adrenergic receptor overexpression induces enhanced cardiac contractility but not hypertrophy. Circ Res 2001;89:343–350.

    Article  PubMed  CAS  Google Scholar 

  73. Milano CA, Dolber PC, Rockman HA, et al. Myocardial expression of a constitutively active alpha lB-adrenergic receptor in transgenic mice induces cardiac hypertrophy. Proc Natl Acad Sci USA 1994;91:10109–10113.

    Article  PubMed  CAS  Google Scholar 

  74. Grupp IL, Lorenz JN, Walsh RA, Boivin GP, Rindt H. Overexpression of alpha1B-adrenergic receptor induces left ventricular dysfunction in the absence of hypertrophy. Am J Physiol 1998;275:H1338–H1350.

    PubMed  CAS  Google Scholar 

  75. Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988;332:411–415.

    Article  PubMed  CAS  Google Scholar 

  76. Clerk A, Pham FH, Fuller SJ, et al. Regulation of mitogen-activated protein kinases in cardiac myocytes through the small G protein Racl. Mol Cell Biol 2001;21:1173–1184.

    Article  PubMed  CAS  Google Scholar 

  77. Yamazaki T, Komuro I, Kudoh S, et al. Endothelin-1 is involved in mechanical stress-induced cardiomyocyte hypertrophy. J Biol Chem 1996;271:3221–3228.

    Article  PubMed  CAS  Google Scholar 

  78. Sakai S, Miyauchi T, Sakurai T, et al. Endogenous endothelin-1 participates in the maintenance of cardiac function in rats with congestive heart failure. Marked increase in endothelin-1 production in the failing heart. Circulation 1996;93:1214–1222.

    PubMed  CAS  Google Scholar 

  79. Sakai S, Miyauchi T, Kobayashi M, Yamaguchi I, Goto K, Sugishita Y. Inhibition of myocardial endothelin pathway improves long-term survival in heart failure. Nature 1996;384:353–355.

    Article  PubMed  CAS  Google Scholar 

  80. Knowlton KU, Michel MC, Itani M, et al. The alpha 1A-adrenergic receptor subtype mediates biochemical, molecular, and morphologic features of cultured myocardial cell hypertrophy. J Biol Chem 1993;268:15374–15380.

    PubMed  CAS  Google Scholar 

  81. Simpson P. Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response. J Clin Invest 1983;72:732–738.

    PubMed  CAS  Google Scholar 

  82. Shubeita HE, McDonough PM, Harris AN, et al. Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy. J Biol Chem 1990;265:20555–20562.

    PubMed  CAS  Google Scholar 

  83. Rockman HA, Ross RS, Harris AN, et al. Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc Natl Acad Sci USA 1991;88:8277–8281.

    Article  PubMed  CAS  Google Scholar 

  84. Akhter SA, Luttrell LM, Rockman HA, Iaccarino G, Lefkowitz RJ, Koch WJ. Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy. Science 1998;280:574–577.

    Article  PubMed  CAS  Google Scholar 

  85. Esposito G, Prasad SV, Rapacciuolo A, Mao L, Koch WJ, Rockman HA. Cardiac overexpression of a G(q) inhibitor blocks induction of extracellular signal-regulated kinase and c-Jun NH(2)-terminal kinase activity in in vivo pressure overload. Circulation 2001;103:1453–1458.

    PubMed  CAS  Google Scholar 

  86. D’Angelo DD, Sakata Y, Lorenz JN, et al. Transgenic Galphaq overexpression induces cardiac contractile failure in mice. Proc Natl Acad Sci USA 1997;94:8121–8126.

    Article  PubMed  CAS  Google Scholar 

  87. Mende U, Kagen A, Cohen A, Aramburu J, Schoen FJ, Neer EJ. Transient cardiac expression of constitutively active Galphaq leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways. Proc Natl Acad Sci USA 1998;95:13893–13898.

    Article  PubMed  CAS  Google Scholar 

  88. Sakata Y, Hoit BD, Liggett SB, Walsh RA, Dorn GW, 2nd. Decompensation of pressure-overload hypertrophy in G alpha q-overexpressing mice. Circulation 1998;97:1488–1495.

    PubMed  CAS  Google Scholar 

  89. Inglese J, Freedman NJ, Koch WJ, Lefkowitz RJ. Structure and mechanism of the G protein-coupled receptor kinases. J Biol Chem 1993;268:23735–23738.

    PubMed  CAS  Google Scholar 

  90. Gros R, Benovic JL, Tan CM, Feldman RD. G-protein-coupled receptor kinase activity is increased in hypertension. J Clin Invest 1997;99:2087–2093.

    PubMed  CAS  Google Scholar 

  91. Choi DJ, Koch WJ, Hunter JJ, Rockman HA. Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase. J Biol Chem 1997;272:17223–17229.

    Article  PubMed  CAS  Google Scholar 

  92. Jaber M, Koch WJ, Rockman H, et al. Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function. Proc Natl Acad Sci USA 1996;93:12974–12979.

    Article  PubMed  CAS  Google Scholar 

  93. Koch WJ, Rockman HA, Samama P, et al. Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science 1995;268:1350–1353.

    Article  PubMed  CAS  Google Scholar 

  94. Koch WJ, Hawes BE, Inglese J, Luttrell LM, Lefkowitz RJ. Cellular expression of the carboxyl terminus of a G protein-coupled receptor kinase attenuates G beta gamma-mediated signaling. J Biol Chem 1994;269:6193–6197.

    PubMed  CAS  Google Scholar 

  95. Freeman K, Lerman I, Kranias EG, et al. Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. J Clin Invest 2001;107: 967–974.

    Article  PubMed  CAS  Google Scholar 

  96. Esposito G, Santana LF, Dilly K, et al. Cellular and functional defects in a mouse model of heart failure. Am J Physiol Heart Circ Physiol 2000;279:H3101–H3112.

    PubMed  CAS  Google Scholar 

  97. Rockman HA, Chien KR, Choi DJ, et al. Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc Natl Acad Sci USA 1998;95:7000–7005.

    Article  PubMed  CAS  Google Scholar 

  98. Arber S, Hunter JJ, Ross J, Jr., et al. MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure. Cell 1997;88:393–403.

    Article  PubMed  CAS  Google Scholar 

  99. Harding VB, Jones LR, Lefkowitz RJ, Koch WJ, Rockman HA. Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure. Proc Natl Acad Sci USA 2001;98:5809–5814.

    Article  PubMed  CAS  Google Scholar 

  100. Freeman K, Colon-Rivera C, Olsson MC, et al. Progression from hypertrophic to dilated cardiomyopathy in mice that express a mutant myosin transgene. Am J Physiol Heart Circ Physiol 2001;280:H151–H159.

    PubMed  CAS  Google Scholar 

  101. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9–13.

    Google Scholar 

  102. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001–2007.

    Google Scholar 

  103. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651–1658.

    Article  PubMed  CAS  Google Scholar 

  104. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med 1996;334:1349–1355.

    Article  PubMed  CAS  Google Scholar 

  105. Rockman HA, Choi DJ, Akhter SA, et al. Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice. J Biol Chem 1998;273:18180–18184.

    Article  PubMed  CAS  Google Scholar 

  106. White DC, Hata JA, Shah AS, Glower DD, Lefkowitz RJ, Koch WJ. Preservation of myocardial beta-adrenergic receptor signaling delays the development of heart failure after myocardial infarction. Proc Natl Acad Sci USA 2000;97:5428–5433.

    Article  PubMed  CAS  Google Scholar 

  107. Shah AS, White DC, Emani S, et al. In vivo ventricular gene delivery of a beta-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction. Circulation 2001;103:1311–1316.

    Article  PubMed  CAS  Google Scholar 

  108. Rockman HA, Choi DJ, Rahman NU, Akhter SA, Lefkowitz RJ, Koch WJ. Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice. Proc Natl Acad Sci USA 1996;93:9954–9959.

    Article  PubMed  CAS  Google Scholar 

  109. Iaccarino G, Rockman HA, Shotwell KF, Tomhave ED, Koch WJ. Myocardial overexpression of GRK3 in transgenic mice: evidence for in vivo selectivity of GRKs. Am J Physiol 1998;275:H1298–H1306.

    PubMed  CAS  Google Scholar 

  110. Rameh LE, Cantley LC. The role of phosphoinositide 3-kinase lipid products in cell function. J Biol Chem 1999;274:8347–8350.

    Article  PubMed  CAS  Google Scholar 

  111. Naga Prasad SV, Esposito G, Mao L, Koch WJ, Rockman HA. Gbetagamma-dependent phosphoinositide 3-Kinase activation in hearts with in vivo pressure overload hypertrophy. J Biol Chem 2000;275:4693–4698.

    Article  PubMed  CAS  Google Scholar 

  112. Naga Prasad SV, Barak LS, Rapacciuolo A, Caron MG, Rockman HA. Agonist-dependent recruitment of phosphoinositide 3-Kinase to the membrane by beta-adrenergic receptor kinase 1. A role in receptor sequestration. J Biol Chem 2001;276:18953–18959.

    Article  PubMed  CAS  Google Scholar 

  113. Naga Prasad SV, Laporte SA, Chamberlain D, Caron MG, Barak L, Rockman HA. Phosphoinositide 3-kinase regulates beta2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/beta-arrestin complex. J Cell Biol 2002; 158:563–75.

    Article  PubMed  CAS  Google Scholar 

  114. Waltenberger J. Modulation of growth factor action: implications for the treatment of cardiovascular diseases. Circulation 1997;96:4083–4094.

    PubMed  CAS  Google Scholar 

  115. Schlessinger J, Ullrich A. Growth factor signaling by receptor tyrosine kinases. Neuron 1992;9:383–391.

    Article  PubMed  CAS  Google Scholar 

  116. Schultz JE, Witt SA, Nieman ML, et al. Fibroblast growth factor-2 mediates pressure-induced hypertrophic response. J Clin Invest 1999;104:709–719.

    PubMed  CAS  Google Scholar 

  117. Calderone A, Takahashi N, Izzo NJ, Jr., Thaik CM, Colucci WS. Pressure-and volume-induced left ventricular hypertrophies are associated with distinct myocyte phenotypes and differential induction of peptide growth factor mRNAs. Circulation 1995;92:2385–2390.

    PubMed  CAS  Google Scholar 

  118. Li RK, Li G, Mickle DA, et al. Overexpression of transforming growth factor-betal and insulin-like growth factor-I in patients with idiopathic hypertrophic cardiomyopathy. Circulation 1997;96:874–881.

    PubMed  CAS  Google Scholar 

  119. Serneri GG, Modesti PA, Boddi M, et al. Cardiac growth factors in human hypertrophy. Relations with myocardial contractility and wall stress. Circ Res 1999;85:57–67.

    PubMed  CAS  Google Scholar 

  120. Bogoyevitch MA, Glennon PE, Andersson MB, et al. Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy. J Biol Chem 1994;269:1110–1119.

    PubMed  CAS  Google Scholar 

  121. Zhang D, Gaussin V, Taffet GE, et al. TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice. Nat Med 2000;6:556–563.

    Article  PubMed  CAS  Google Scholar 

  122. Villarreal FJ, Dillmann WH. Cardiac hypertrophy-induced changes in mRNA levels for TGF-beta 1, fibronectin, and collagen. Am J Physiol 1992;262:H1861–H1866.

    PubMed  CAS  Google Scholar 

  123. Takahashi N, Calderone A, Izzo NJ, Jr., Maki TM, Marsh JD, Colucci WS. Hypertrophic stimuli induce transforming growth factor-beta 1 expression in rat ventricular myocytes. J Clin Invest 1994;94:1470–1476.

    PubMed  CAS  Google Scholar 

  124. Parker TG, Packer SE, Schneider MD. Peptide growth factors can provoke “fetal” contractile protein gene expression in rat cardiac myocytes. J Clin Invest 1990;85:507–514.

    PubMed  CAS  Google Scholar 

  125. Sivasubramanian N, Coker ML, Kurrelmeyer KM, et al. Left ventricular remodeling in transgenic mice with cardiac restricted overexpression of tumor necrosis factor. Circulation 2001:104:826–831.

    Article  PubMed  CAS  Google Scholar 

  126. Kishimoto T, Taga T, Akira S. Cytokine signal transduction. Cell 1994;76:253–262.

    Article  PubMed  CAS  Google Scholar 

  127. Yamauchi-Takihara K, Kishimoto T. A novel role for STAT3 in cardiac remodeling. Trends Cardiovasc Med 2000;10:298–303.

    Article  PubMed  CAS  Google Scholar 

  128. Hirano T, Nakajima K, Hibi M. Signaling mechanisms through gpl30: a model of the cytokine system. Cytokine Growth Factor Rev 1997;8:241–252.

    Article  PubMed  CAS  Google Scholar 

  129. Hirota H, Chen J, Betz UA, et al. Loss of a gpl30 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell 1999;97:189–198.

    Article  PubMed  CAS  Google Scholar 

  130. Hirota H, Yoshida K, Kishimoto T, Taga T. Continuous activation of gpl30, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Proc Natl Acad Sci USA 1995;92:4862–4866.

    Article  PubMed  CAS  Google Scholar 

  131. Uozumi H, Hiroi Y, Zou Y, et al. gpl30 plays a critical role in pressure overload-induced cardiac hypertrophy. J Biol Chem 2001;276:23115–23119.

    Article  PubMed  CAS  Google Scholar 

  132. Pennica D, King KL, Shaw KJ, et al. Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. Proc Natl Acad Sci USA 1995;92:1142–1146.

    Article  PubMed  CAS  Google Scholar 

  133. Sheng Z, Knowlton K, Chen J, Hoshijima M, Brown JH, Chien KR. Cardiotrophin 1 (CT-1) inhibition of cardiac myocyte apoptosis via a mitogen-activated protein kinase-dependent pathway. Divergence from downstream CT-1 signals for myocardial cell hypertrophy. J Biol Chem 1997;272:5783–5791.

    Article  PubMed  CAS  Google Scholar 

  134. Habib FM, Springall DR, Davies GJ, Oakley CM, Yacoub MH, Polak JM. Tumour necrosis factor and inducible nitric oxide synthase in dilated cardiomyopathy. Lancet 1996;347:1151–1155.

    Article  PubMed  CAS  Google Scholar 

  135. Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990;323:236–241.

    Article  PubMed  CAS  Google Scholar 

  136. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 1996;27:1201–1206.

    Article  PubMed  CAS  Google Scholar 

  137. Kubota T, Miyagishima M, Alvarez RJ, et al. Expression of proinflammatory cytokines in the failing human heart: comparison of recent-onset and end-stage congestive heart failure. J Heart Lung Transplant 2000;19:819–824.

    Article  PubMed  CAS  Google Scholar 

  138. Sack MN, Smith RM, Opie LH. Tumor necrosis factor in myocardial hypertrophy and ischaemia—an anti-apoptotic perspective. Cardiovasc Res 2000;45:688–695.

    Article  PubMed  CAS  Google Scholar 

  139. Kadokami T, McTiernan CF, Kubota T, Frye CS, Feldman AM. Sex-related survival differences in murine cardiomyopathy are associated with differences in TNF-receptor expression. J Clin Invest 2000;106:589–597.

    PubMed  CAS  Google Scholar 

  140. Kubota T, McTiernan CF, Frye CS, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ Res 1997;81:627–635.

    PubMed  CAS  Google Scholar 

  141. Li X, Moody MR, Engel D, et al. Cardiac-specific overexpression of tumor necrosis factor-alpha causes oxidative stress and contractile dysfunction in mouse diaphragm. Circulation 2000;102:1690–1696.

    PubMed  CAS  Google Scholar 

  142. Seger R, Krebs EG. The MAPK signaling cascade. Faseb J 1995;9:726–735.

    PubMed  CAS  Google Scholar 

  143. Garrington TP, Johnson GL. Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol 1999;11:211–218.

    Article  PubMed  CAS  Google Scholar 

  144. Davis RJ. The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 1993;268:14553–14556.

    PubMed  CAS  Google Scholar 

  145. Force T, Pombo CM, Avruch JA, Bonventre JV, Kyriakis JM. Stress-activated protein kinases in cardiovascular disease. Circ Res 1996;78:947–953.

    PubMed  CAS  Google Scholar 

  146. Ramirez MT, Sah VP, Zhao XL, Hunter JJ, Chien KR, Brown JH. The MEKK-JNK pathway is stimulated by alphal-adrenergic receptor and ras activation and is associated with in vitro and in vivo cardiac hypertrophy. J Biol Chem 1997;272:14057–14061.

    Article  PubMed  CAS  Google Scholar 

  147. Rapacciuolo A, Esposito G, Caron K, Mao L, Thomas SA, Rockman HA. Important role of endogenous norepinephrine and epinephrine in the development of in vivo pressure-overload cardiac hypertrophy. J Am Coll Cardiol 2001;38:876–882.

    Article  PubMed  CAS  Google Scholar 

  148. Boulton TG, Nye SH, Robbins DJ, et al. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGR Cell 1991;65:663–675.

    Article  PubMed  CAS  Google Scholar 

  149. Sadoshima J, Izumo S. Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: potential involvement of an autocrine/paracrine mechanism. Embo J 1993;12:1681–1692.

    PubMed  CAS  Google Scholar 

  150. Bogoyevitch MA, Ketterman AJ, Sugden PH. Cellular stresses differentially activate c-Jun N-terminal protein kinases and extracellular signal-regulated protein kinases in cultured ventricular myocytes. J Biol Chem 1995;270:29710–29717.

    Article  PubMed  CAS  Google Scholar 

  151. Bueno OF, De Windt LJ, Tymitz KM, et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. Embo J 2000;19:6341–6350.

    Article  PubMed  CAS  Google Scholar 

  152. Wang LX, Ideishi M, Yahiro E, Urata H, Arakawa K, Saku K. Mechanism of the cardioprotective effect of inhibition of the renin-angiotensin system on ischemia/reperfusion-induced myocardial injury. Hypertens Res 2001;24:179–187.

    Article  PubMed  CAS  Google Scholar 

  153. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell 2000;103:239–252.

    Article  PubMed  CAS  Google Scholar 

  154. Coso OA, Chiariello M, Yu JC, et al. The small GTP-binding proteins Racl and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 1995;81:1137–1146.

    Article  PubMed  CAS  Google Scholar 

  155. Minden A, Lin A, Claret FX, Abo A, Karin M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell 1995;81:1147–1157.

    Article  PubMed  CAS  Google Scholar 

  156. Gupta S, Barrett T, Whitmarsh AJ, et al. Selective interaction of JNK protein kinase isoforms with transcription factors. Embo J 1996;15:2760–2770.

    PubMed  CAS  Google Scholar 

  157. Nemoto S, Sheng Z, Lin A. Opposing effects of Jun kinase and p38 mitogen-activated protein kinases on cardiomyocyte hypertrophy. Mol Cell Biol 1998;18:3518–3526.

    PubMed  CAS  Google Scholar 

  158. Kudoh S, Komuro I, Mizuno T, et al. Angiotensin II stimulates c-Jun NH2-terminal kinase in cultured cardiac myocytes of neonatal rats. Circ Res 1997;80:139–146.

    PubMed  CAS  Google Scholar 

  159. Wang Y, Su B, Sah VP, Brown JH, Han J, Chien KR. Cardiac hypertrophy induced by mitogen-activated protein kinase kinase 7, a specific activator for c-Jun NH2-terminal kinase in ventricular muscle cells. J Biol Chem 1998;273:5423–5426.

    Article  PubMed  CAS  Google Scholar 

  160. Choukroun G, Hajjar R, Fry S, et al. Regulation of cardiac hypertrophy in vivo by the stress-activated protein kinases/c-Jun NH(2)-terminal kinases. J Clin Invest 1999;104:391–398.

    PubMed  CAS  Google Scholar 

  161. Jiang Y, Gram H, Zhao M, et al. Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. J Biol Chem 1997;272:30122–30128.

    Article  PubMed  CAS  Google Scholar 

  162. Paul A, Wilson S, Belham CM, et al. Stress-activated protein kinases: activation, regulation and function. Cell Signal 1997;9:403–410.

    Article  PubMed  CAS  Google Scholar 

  163. Lazou A, Sugden PH, Clerk A. Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs) by the G-protein-coupled receptor agonist phenylephrine in the perfused rat heart. Biochem J 1998;332:459–465.

    PubMed  CAS  Google Scholar 

  164. Meloche S, Landry J, Huot J, Houle F, Marceau F, Giasson E. p38 MAP kinase pathway regulates angiotensin II-induced contraction of rat vascular smooth muscle. Am J Phy siol Heart Circ Physiol 2000;279:H741–H751.

    CAS  Google Scholar 

  165. Wang Y, Huang S, Sah VP, et al. Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. J Biol Chem 1998;273:2161–2168.

    Article  PubMed  CAS  Google Scholar 

  166. Zechner D, Thuerauf DJ, Hanford DS, McDonough PM, Glembotski CC. A role for the p38 mitogen-activated protein kinase pathway in myocardial cell growth, sarcomeric organization, and cardiac-specific gene expression. J Cell Biol 1997;139:115–127.

    Article  PubMed  CAS  Google Scholar 

  167. Izumi Y, Kim S, Murakami T, Yamanaka S, Iwao H. Cardiac mitogen-activated protein kinase activities are chronically increased in stroke-prone hypertensive rats. Hypertension 1998;31:50–56.

    PubMed  CAS  Google Scholar 

  168. Izumi Y, Kim S, Zhan Y, Namba M, Yasumoto H, Iwao H. Important role of angiotensin II-mediated c-Jun NH(2)-terminal kinase activation in cardiac hypertrophy in hypertensive rats. Hypertension 2000;36:511–516.

    PubMed  CAS  Google Scholar 

  169. Cook SA, Sugden PH, Clerk A. Activation of c-Jun N-terminal kinases and p38-mitogen-activated protein kinases in human heart failure secondary to ischaemic heart disease. J Mol Cell Cardiol 1999;31:1429–1434.

    Article  PubMed  CAS  Google Scholar 

  170. Haq S, Choukroun G, Lim H, et al. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure. Circulation 2001;103:670–677.

    PubMed  CAS  Google Scholar 

  171. Imada K, Leonard WJ. The Jak-STAT pathway. Mol Immunol 2000;37:1–11.

    Article  PubMed  CAS  Google Scholar 

  172. Leonard WJ. Role of Jak kinases and STATs in cytokine signal transduction. Int J Hematol 2001;73:271–277.

    Article  PubMed  CAS  Google Scholar 

  173. Igaz P, Toth S, Falus A. Biological and clinical significance of the JAK-STAT pathway; lessons from knockout mice. Inflamm Res 2001;50:435–441.

    Article  PubMed  CAS  Google Scholar 

  174. Kunisada K, Negoro S, Tone E, et al. Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy. Proc Natl Acad Sci USA 2000:97:315–319.

    Article  PubMed  CAS  Google Scholar 

  175. Crabtree GR. Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT. Cell 1999;96:611–614.

    Article  PubMed  CAS  Google Scholar 

  176. Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 1997;15:707–747.

    Article  PubMed  CAS  Google Scholar 

  177. Kolodziejczyk SM, Wang L, Balazsi K, DeRepentigny Y, Kothary R, Megeney LA. MEF2 is upregulated during cardiac hypertrophy and is required for normal post-natal growth of the myocardium. Curr Biol 1999;9:1203–1206.

    Article  PubMed  CAS  Google Scholar 

  178. Molkentin JD, Lu JR, Antos CL, et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 1998;93: 215–228.

    Article  PubMed  CAS  Google Scholar 

  179. Klee CB, Ren H, Wang X. Regulation of the calmodulin-stimulated protein phosphatase, calcineurin. J Biol Chem 1998;273:13367–13370.

    Article  PubMed  CAS  Google Scholar 

  180. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–1346.

    PubMed  CAS  Google Scholar 

  181. Cambien F, Evans A. Angiotensin I converting enzyme gene polymorphism and coronary heart disease. Eur Heart J 1995;16:13–22.

    PubMed  Google Scholar 

  182. Cambien F, Poirier O, Lecerf L, et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992;359:641–644.

    Article  PubMed  CAS  Google Scholar 

  183. Andersson B, Sylven C. The DD genotype of the angiotensin-converting enzyme gene is associated with increased mortality in idiopathic heart failure. J Am Coll Cardiol 1996;28:162–167.

    Article  PubMed  CAS  Google Scholar 

  184. McNamara DM, Holubkov R, Janosko K, et al. Pharmacogenetic interactions between beta-blocker therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure. Circulation 2001;103:1644–1648.

    PubMed  CAS  Google Scholar 

  185. Loh E, Rebbeck TR, Mahoney PD, DeNofrio D, Swain JL, Holmes EW. Common variant in AMPD1 gene predicts improved clinical outcome in patients with heart failure. Circulation 1999;99:1422–1425.

    PubMed  CAS  Google Scholar 

  186. Podlowski S, Wenzel K, Luther HP, et al. Betal-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy? J Mol Med 2000;78:87–93.

    Article  PubMed  CAS  Google Scholar 

  187. Green SA, Cole G, Jacinto M, Innis M, Liggett SB. A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem 1993;268:23116–23121.

    PubMed  CAS  Google Scholar 

  188. Liggett SB, Wagoner LE, Craft LL, et al. The Ile 164 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 1998;102:1534–1539.

    PubMed  CAS  Google Scholar 

  189. Wagoner LE, Craft LL, Singh B, et al. Polymorphisms of the beta(2)-adrenergic receptor determine exercise capacity in patients with heart failure. Circ Res 2000;86:834–840.

    PubMed  CAS  Google Scholar 

  190. Collins FS. Shattuck lecture-medical and societal consequences of the Human Genome Project. N Engl J Med 1999;341:28–37.

    Article  PubMed  CAS  Google Scholar 

  191. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 1996;27:1202–1206.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Duke University Medical Center, Durham, NC

    Shayela Suvarna PhD, Liza Barki-Harrington PhD, Miwako Suzuki MD, PhD & Philippe Le Corvoisier MD

  2. Departments of Medicine, Cell Biology, and Genetics, Duke University Medical Center, Durham, NC

    Howard A. Rockman MD

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  1. Shayela Suvarna PhD
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  2. Liza Barki-Harrington PhD
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  3. Miwako Suzuki MD, PhD
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  4. Philippe Le Corvoisier MD
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  5. Howard A. Rockman MD
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  1. Department of Medicine, UNC School of Medicine, Chapell Hill, NC

    Marschall S. Runge MD, PhD

  2. Carolina Cardiovascular Biology Center, Chapel Hill, NC

    Cam Patterson MD

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Suvarna, S., Barki-Harrington, L., Suzuki, M., Le Corvoisier, P., Rockman, H.A. (2005). Receptor-Signaling Pathways in Heart Failure. In: Runge, M.S., Patterson, C. (eds) Principles of Molecular Cardiology. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59259-878-6_8

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