Molecular determinants of myocardial hypertrophy and failure: Alternative pathways for beneficial and maladaptive hypertrophy

European Heart Journal

Volumn 24, Issue 10, 2003, Pages 883-896

  Lips, Daniel J ^a   DeWindt, Leon J ^a   Van Kraaij, Dave J W ^c   Doevendans, Pieter A ^b  

^a MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^c NONE

Author keywords

Apoptosis; Calcium handling; Fibrosis; Gene expression; Heart failure; Hypertrophy

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE;

ANGINA PECTORIS; APOPTOSIS; CALCIUM CELL LEVEL; CARDIOVASCULAR RISK; DIABETES MELLITUS; DISEASE ASSOCIATION; FIBROSIS; HEART FAILURE; HEART INFARCTION; HEART STRESS; HEART VENTRICLE HYPERTROPHY; HEART VENTRICLE WALL; HUMAN; HYPERTENSION; MALADJUSTMENT; MOLECULAR BIOLOGY; PRIORITY JOURNAL; REVIEW; SYMPTOMATOLOGY; TREATMENT OUTCOME; VALVULAR HEART DISEASE;

APOPTOSIS; CALCIUM; FEMALE; FIBROSIS; HEART FAILURE, CONGESTIVE; HUMANS; HYPERTROPHY, LEFT VENTRICULAR; INTRACELLULAR FLUID; MALE; MUSCLE CELLS; MUTATION; RISK FACTORS; SEX FACTORS;

EID: 0037991449     PISSN: 0195668X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0195-668X(02)00829-1     Document Type: Review

References (132)

1. Mosterd A, Hoes AW, de Bruyne MC et al. Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study. Eur Heart J 1999;20:447-55.
2. Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: global burden of disease study [see comments]. Lancet 1997;349:1436-42.
3. Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: global burden of disease study [see comments]. Lancet 1997;349:1269-76.
4. Dargie HJ, McMurray JJ, McDonagh TA. Heart failure-implications of the true size of the problem. J Intern Med 1996;239:309-15.
5. Maron BJ. Hypertrophic cardiomyopathy [published erratum appears in Lancet 1997 Nov 1;350(9087):1330]. Lancet 1997;350:127-33.
6. Van Kraaij D, Van Pol P, Ruiters AW et al. Diagnosing diastolic heart failure. Eur J Heart Fail 2002;4:419-30.
7. Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001;22:1527-60.
8. Braunwald E. Heart disease: a textbook of cardiovascular medicine. 5th ed. Philadelphia: WB Saunders, 1997.
9. James MA, Saadeh AM, Jones JV. Wall stress and hypertension [in process citation]. J Cardiovasc Risk 2000;7:187-90.
10. 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 [published erratum appears in Proc Natl Acad Sci U S A 1991 Nov 1;88(21):9907]. Proc Natl Acad Sci U S A 1991;88:8277-81.
11. Van der laarse ARC, Van Wamel JET, Van Gilst WH et al. Molecular aspects of cardiac hypertrophy and heart failure. Cardiologie 1998.
12. Esposito G, Rapacciuolo A, 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.
13. Matthew J, Sleight P, Lonn E et al. Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril. Circulation 2001;104:1615-21.
14. Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation 2000;102:470-9.
15. Obayashi T, Hattori K, Sugiyama S et al. Point mutations in mitochondrial DNA in patients with hypertrophic cardiomyopathy. Am Heart J 1992;124:1263-9.
16. Maron BJ, Gardin JM, Flack JM et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA study. Coronary artery risk development in (young) adults [see comments]. Circulation 1995;92:785-9.
17. Olson TM, Michels VV, Thibodeau SN et al. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science 1998;280:750-2.
18. Satoh M, Takahashi M, Sakamoto T et al. Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification of a novel disease gene. Biochem Biophys Res Commun 1999;262:411-7.
19. Watkins H, Seidman JG, Seidman CE. Familial hypertrophic cardiomyopathy: a genetic model of cardiac hypertrophy. Hum Mol Genet 1995;4:1721-7.
20. Yamazaki T, Komuro I, Yazaki Y. Role of the reninangiotensin system in cardiac hypertrophy. Am J Cardiol 1999;83:53H-7H.
21. Baker KM, Chernin MI, Wixson SK et al. Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats. Am J Physiol 1990;259:H324-32.
22. Kijima K, Matsubara H, Murasawa S et al. Mechanical stretch induces enhanced of angiotensin II receptor subtypes in neonatal rat cardiac myocytes. Circ Res 1996;79:887-97.
23. Mascareno E, Dhar M, Siddiqui MA. Signal transduction and activator of transcription (STAT) protein-dependent activation of angiotensinogen promoter: a cellular signal for hypertrophy in cardiac muscle. Proc Natl Acad Sci U S A 1998;95:5590-4.
24. Sadoshima J, Izumo S. Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res 1993;73:413-23.
25. Sadoshima J, Xu Y, Slayter HS et al. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993;75:977-84.
26. Arai M, Yoguchi A, Iso T et al. Endothelin-1 and its binding sites are upregulated in pressure overload cardiac hypertrophy. Am J Physiol 1995;268:H2084-91.
27. Ito H, Hiroe M, Hirata Y et al. Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload. Circulation 1994;89:2198-203.
28. Murphree SS, Saffitz JE. Distribution of beta-adrenergic receptors in failing human myocardium. Implications for mechanisms of down-regulation. Circulation 1989;79:1214-25.
29. Tse J, Huang MW, Leone RJ et al. Down regulation of myocardial beta1-adrenoceptor signal transduction system in pacing-induced failure in dogs with aortic stenosis-induced left ventricular hypertrophy. Mol Cell Biochem 2000;205:67-73.
30. 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;273:18180-4.
31. Bohm M, Flesch M, Schnabel P. Beta-adrenergic signal transduction in the failing and hypertrophied myocardium. J Mol Med 1997;75:842-8.
32. Rush JE, Rajfer SI. Theoretical basis for the use of angiotensin II antagonists in the treatment of heart failure. J Hypertens Suppl 1993;11:S69-71.
33. Regitz-Zagrosek V, Neuss M, Fleck E. Effects of angiotensin receptor antagonists in heart failure: clinical and experimental aspects. Eur Heart J 1995;16 Suppl N:86-91.
34. Senzaki H, Paolocci N, Gluzband YA et al. Beta-blockade prevents sustained metalloproteinase activation and diastolic stiffening induced by angiotensin II combined with evolving cardiac dysfunction. Circ Res 2000;86:807-15.
35. 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;269:1110-9.
36. Kaddoura S, Firth JD, Boheler KR et al. Endothelin-1 is involved in norepinephrine-induced ventricular hypertrophy in vivo. Acute effects of bosentan, an orally active, mixed endothelin ETA and ETB receptor antagonist. Circulation 1996;93:2068-79.
37. Pennica D, King KL, Shaw KJ et al. Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. Proc Natl Acad Sci U S A 1995;92:1142-6.
38. Parker TG, Chow KL, Schwartz RJ et al. Positive and negative control of the skeletal alpha-actin promoter in cardiac muscle. A proximal serum response element is sufficient for induction by basic fibroblast growth factor (FGF) but not for inhibition by acidic FGF. J Biol Chem 1992;267:3343-50.
39. Parker TG, Packer SE, Schneider MD. Peptide growth factors can provoke 'fetal' contractile protein gene expression in rat cardiac myocytes. J Clin Invest 1990;85:507-14.
40. Ito H, Hiroe M, Hirata Y et al. Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation 1993;87:1715-21.
41. Ito H, Hirata Y, Adachi S et al. Endothelin-1 is an autocrine/paracrine factor in the mechanism of angiotensin II-induced hypertrophy in cultured rat cardiomyocytes. J Clin Invest 1993;92:398-403.
42. Kim NN, Villarreal FJ, Printz MP et al. Trophic effects of angiotensin II on neonatal rat cardiac myocytes are mediated by cardiac fibroblasts. Am J Physiol 1995;269:E426-37.
43. Lavandero S, Foncea R, Perez V et al. Effect of inhibitors of signal transduction on IGF-1-induced protein synthesis associated with hypertrophy in cultured neonatal rat ventricular myocytes. FEBS Lett 1998;422:193-6.
44. Van Eickels M, Grohe C, Cleutjens JPM et al. 17Beta-estradiol attenuates the development of pressure-overload hypertrophy. Circulation 2001;104:1419-23.
45. Hayward CS, Webb CM, Collins P. Effect of sex hormones on cardiac mass. Lancet 2001;357:1354-6.
46. Nuedling S, Kahlert S, Loebbert K et al. Differential effects of 17beta-estradiol on mitogen-activated protein kinase pathways in rat cardiomyocytes. FEBS Lett 1999;454:271-6.
47. Grohe C, Kahlert S, Lobbert K et al. Expression of oestrogen receptor alpha and beta in rat heart: role of local oestrogen synthesis. J Endocrinol 1998;156:R1-7.
48. Grohe C, Kahlert S, Lobbert K et al. Cardiac myocytes and fibroblasts contain functional estrogen receptors. FEBS Lett 1997;416:107-12.
49. Babiker FA, De Windt LJ, Bronsaer RJP et al. Estrogen antagonizes cardiomyocyte hypertrophy by autocrine/paracrine stimulation of a guanyly cyclase-A receptor-cGMP-dependent protein kinase pathway. Circulation 2001;104:77.
50. Lin KF, Chao J, Chao L. Atrial natriuretic peptide gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in salt-sensitive rats. Hum Gene Ther 1998;9:1429-38.
51. Hilal-Dandan R, Ramirez MT, Villegas S et al. Endothelin ETA receptor regulates signaling and ANF gene expression via multiple G protein-linked pathways. Am J Physiol 1997;272:H130-7.
52. Milano CA, Dolber PC, Rockman HA et al. Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. Proc Natl Acad Sci U S A 1994;91:10109-13.
53. D'Angelo DD, Sakata Y, Lorenz JN et al. Transgenic Galphaq overexpression induces cardiac contractile failure in mice. Proc Natl Acad Sci U S A 1997;94:8121-6.
54. Clerk A, Bogoyevitch MA, Anderson MB et al. Differential activation of protein kinase C isoforms by endothelin-1 and phenylephrine and subsequent stimulation of p42 and p44 mitogen-activated protein kinases in ventricular myocytes cultured from neonatal rat hearts. J Biol Chem 1994;269:32848-57.
55. Denhardt DT. Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell: the potential for multiplex signalling. Biochem J 1996;318:729-47.
56. Thorburn J, Xu S, Thorburn A. MAP kinase- and Rho-dependent signals interact to regulate gene expression but not actin morphology in cardiac muscle cells. Embo J 1997;16:1888-900.
57. 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;19:6341-50.
58. Bueno OF, De Windt LJ, Lim HW et al. The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo. Circ Res 2001;88:88-96.
59. Esposito G, Santana LF, Dilly K et al. Cellular and functional defects in a mouse model of heart failure [in process citation]. Am J Physiol Heart Circ Physiol 2000;279:H3101-12.
60. Nicol RL, Frey N, Pearson G et al. Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy. Embo J 2001;20:2757-67.
61. 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;6:556-63.
62. Ng DC, Long CS, Bogoyevitch MA. A role for the ERK and p38 MAPKs in Interleukin-1beta-stimulated delayed STAT3 activation, ANF expression and cardiac myocyte morphology. J Biol Chem 2001;29:29.
63. Hayashida W, Kihara Y, Yasaka A et al. Stage-specific differential activation of mitogen-activated protein kinases in hypertrophied and failing rat hearts. J Mol Cell Cardiol 2001;33:733-44.
64. Fischer TA, Ludwig S, Flory E et al. Activation of cardiac c-Jun NH(2)-terminal kinases and p38-mitogen-activated protein kinases with abrupt changes in hemodynamic load. Hypertension 2001;37:1222-8.
65. 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;31:1429-34.
66. Sheng Z, Knowlton K, Chen J et al. 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;272:5783-91.
67. Kodama H, Fukuda K, Pan J et al. Biphasic activation of the JAK/STAT pathway by angiotensin II in rat cardiomyocytes. Circ Res 1998;82:244-50.
68. Pan J, Fukuda K, Kodama H et al. Role of angiotensin II in activation of the JAK/STAT pathway induced by acute pressure overload in the rat heart. Circ Res 1997;81:611-7.
69. De Windt LJ, Lim HW, Haq S et al. Calcineurin promotes protein kinase C and c-Jun NH2-terminal kinase activation in the heart. Cross-talk between cardiac hypertrophic signaling pathways. J Biol Chem 2000;275:13571-9.
70. De Windt LJ, Lim HW, Taigen T et al. Calcineurin-mediated hypertrophy protects cardiomyocytes from apoptosis in vitro and in vivo: an apoptosis-independent model of dilated heart failure. Circ Res 2000;86:255-63.
71. Lim HW, De Windt LJ, Steinberg L et al. Calcineurin expression, activation, and function in cardiac pressure-overload hypertrophy. Circulation 2000;101:2431-7.
72. Lim HW, De Windt LJ, Mante J et al. Reversal of cardiac hypertrophy in transgenic disease models by calcineurin inhibition. J Mol Cell Cardiol 2000;32:697-709.
73. Ramirez MT, Zhao XL, Schulman H et al. The nuclear deltaB isoform of Ca2+/calmodulin-dependent protein kinase II regulates atrial natriuretic factor gene expression in ventricular myocytes. J Biol Chem 1997;272:31203-8.
74. Taigen T, De Windt LJ, Lim HW et al. Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A 2000;97:1196-201.
75. 2+ handling in isolated rat myocardium. Am J Physiol 1998;274:H1361-70.
76. 2+ dynamics in single cardiac myocytes from renovascular hypertensive rats. Am J Physiol 1991;260:C327-37.
77. Qi M, Shannon TR, Euler DE et al. Downregulation of sarcoplasmic reticulum Ca(2+)-ATPase during progression of left ventricular hypertrophy. Am J Physiol 1997;272:H2416-24.
78. Kiss E, Ball NA, Kranias EG et al. Differential changes in cardiac phospholamban and sarcoplasmic reticular Ca(2+)-ATPase protein levels. Effects on Ca2+ transport and mechanics in compensated pressure-overload hypertrophy and congestive heart failure. Circ Res 1995;77:759-64.
79. de la Bastie D, Levitsky D, Rappaport L et al. Function of the sarcoplasmic reticulum and expression of its Ca2(+)-ATPase gene in pressure overload-induced cardiac hypertrophy in the rat. Circ Res 1990;66:554-64.
80. Bailey BA, Houser SR. Sarcoplasmic reticulum-related changes in cytosolic calcium in pressure overload-induced feline LV hypertrophy. Am J Physiol 1993;265:H2009-16.
81. Arai M, Matsui H, Periasamy M. Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circ Res 1994;74:555-64.
82. Nediani C, Formigli L, Perna AM et al. Early changes induced in the left ventricle by pressure overload. An experimental study on swine heart. J Mol Cell Cardiol 2000;32:131-42.
83. Movsesian MA, Schwinger RH. Calcium sequestration by the sarcoplasmic reticulum in heart failure [see comments]. Cardiovasc Res 1998;37:352-9.
84. Munch G, Bolck B, Hoischen S et al. Unchanged protein expression of sarcoplasmic reticulum Ca2+-ATPase, phospholamban, and calsequestrin in terminally failing human myocardium. J Mol Med 1998;76:434-41.
85. Schwinger RH, Bohm M, Schmidt U et al. Unchanged protein levels of SERCA II and phospholamban but reduced Ca2+ uptake and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum from dilated cardiomyopathy patients compared with patients with nonfailing hearts. Circulation 1995;92:3220-8.
86. Schwinger RH, Bolck B, Munch G et al. cAMP-dependent protein kinase A-stimulated sarcoplasmic reticulum function in heart failure. Ann N Y Acad Sci 1998;853:240-50.
87. Schwinger RH, Munch G, Bolck B et al. Reduced Ca(2+)-sensitivity of SERCA 2a in failing human myocardium due to reduced serin-16 phospholamban phosphorylation. J Mol Cell Cardiol 1999;31:479-91.
88. Arber S, Halder G, Caroni P. Muscle LIM protein, a novel essential regulator of myogenesis, promotes myogenic differentiation. Cell 1994;79:221-31.
89. Arber S, Caroni P. Specificity of single LIM motifs in targeting and LIM/LIM interactions in situ. Genes Dev 1996;10:289-300.
90. 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.
91. Kong Y, Flick MJ, Kudla AJ et al. Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD. Mol Cell Biol 1997;17:4750-60.
92. Schneider AG, Sultan KR, Pette D. Muscle LIM protein: expressed in slow muscle and induced in fast muscle by enhanced contractile activity. Am J Physiol 1999;276:C900-6.
93. Mahaney JE, Autry JM, Jones LR. Kinetics studies of the cardiac Ca-ATPase expressed in Sf21 cells: new insights on Ca-ATPase regulation by phospholamban. Biophys J 2000;78:1306-23.
94. Luo W, Grupp IL, Harrer J et al. Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation. Circ Res 1994;75:401-9.
95. Luo W, Chu G, Sato Y et al. Transgenic approaches to define the functional role of dual site phospholamban phosphorylation. J Biol Chem 1998;273:4734-9.
96. Hoit BD, Khoury SF, Kranias EG, Ball N, Walsh RA. In vivo echocardiographic detection of enhanced left ventricular function in gene-targeted mice with phospholamban deficiency. Circ Res 1995;77:632-7.
97. Kadambi VJ, Ponniah S, Harrer JM, Hoit BD, Dorn GW 2nd, Walsh RA et al. Cardiac-specific overexpression of phospholamban alters calcium kinetics and resultant cardiomyocyte mechanics in transgenic mice. J Clin Invest 1996;97:533-9.
98. Minamisawa S, Hoshijima M, Chu G et al. Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell 1999;99:313-22.
99. Schwinger RH, Brixius K, Savvidou-Zaroti P, Bolck B, Zobel C, Frank K et al. The enhanced contractility in phospholamban deficient mouse hearts is not associated with alterations in (Ca2+)-sensitivity or myosin ATPase-activity of the contractile proteins. Basic Res Cardiol 2000;95:12-8.
100. Saraste A, Pulkki K. Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 2000;45:528-37.
101. Brunet CL, Gunby RH, Benson RS, Hickman JA, Watson AJ, Brady G. Commitment to cell death measured by loss of clonogenicity is separable from the appearance of apoptotic markers. Cell Death Differ 1998;5:107-15.
102. Foncea R, Galvez A, Perez V et al. Extracellular regulated kinase, but not protein kinase C, is an antiapoptotic signal of insulin-like growth factor-1 on cultured cardiac myocytes. Biochem Biophys Res Commun 2000;273:736-44.
103. Lips DJ, Bueno OF, Wilkins BJ et al. MEK1-ERK1/2-regulated signaling pathway plays a decisive cardioprotective role in ischemia-reperfusion injury. 2002 (submitted for publication).
104. Hasegawa K, Iwai-Kanai E, Sasayama S. Neurohormonal regulation of myocardial cell apoptosis during the development of heart failure. J Cell Physiol 2001;186:11-8.
105. Narula J, Kolodgie FD, Virmani R. Apoptosis and cardiomyopathy. Curr Opin Cardiol 2000;15:183-8.
106. Susin SA, Zamzami N, Castedo M et al. Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J Exp Med 1996;184:1331-41.
107. Joza N, Susin SA, Daugas E et al. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature 2001;410:549-54.
108. Hisatomi T, Sakamoto T, Murata T et al. Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo. Am J Pathol 2001;158:1271-8.
109. Hofstra L, Liem IH, Dumont E et al. Visualisation of cell death in vivo in patients with acute myocardial infarction. Lancet 2000;356:209-12.
110. Dumont E, Reutelingsperger CP, Smits JF et al. Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart. Nat Med 2001;7:1352-5.
111. Thornberry NA, Lazebnik Y. Caspases: enemies within. Science 1998;281:1312-6.
112. Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science 1998;281:1305-8.
113. Chen Z, Chua CC, Ho YS, Hamdy RC, Chua BH. Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R injury in transgenic mice. Am J Physiol Heart Circ Physiol 2001;280:H2313-20.
114. Condorelli G, Morisco C, Stassi G et al. Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat. Circulation 1999;99:3071-8.
115. Fearnhead HO, Rodriguez J, Govek EE et al. Oncogene-dependent apoptosis is mediated by caspase-9. Proc Natl Acad Sci U S A 1998;95:13664-9.
116. Soengas MS, Alarcon RM, Yoshida H et al. Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science 1999;284:156-9.
117. Liu X, Li P, Widlak P et al. The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis. Proc Natl Acad Sci U S A 1998;95:8461-6.
118. Enari M, Sakahira H, Yokoyama H et al. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 1998;391:43-50.
119. Narula J, Pandey P, Arbustini E et al. Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy. Proc Natl Acad Sci U S A 1999;96:8144-9.
120. Narula J, Hajjar RJ, Dec GW. Apoptosis in the failing heart. Cardiol Clin 1998;16:691-710.
121. Suzuki K, Kostin S, Person V, Elsasser A, Schaper J. Time course of the apoptotic cascade and effects of caspase inhibitors in adult rat ventricular cardiomyocytes. J Mol Cell Cardiol 2001;33:983-94.
122. Vescovo G, Volterrani M, Zennaro R et al. Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes. Heart 2000;84:431-7.
123. Kajstura J, Leri A, Finato N et al. Myocyte proliferation in end-stage cardiac failure in humans. Proc Natl Acad Sci U S A 1998;95:8801-5.
124. Beltrami AP, Urbanek K, Kajstura J et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001;344:1750-7.
125. Burlew BS, Weber KT. Connective tissue and the heart. Functional significance and regulatory mechanisms. Cardiol Clin 2000;18:435-42.
126. Lijnen P, Petrov V. Induction of cardiac fibrosis by aldosterone. J Mol Cell Cardiol 2000;32:865-79.
127. Lijnen PJ, Petrov VV, Fagard RH. Induction of cardiac fibrosis by angiotensin II. Methods Find Exp Clin Pharmacol 2000;22:709-23.
128. Schnee JM, Hsueh WA. Angiotensin II adhesion, and cardiac fibrosis. Cardiovasc Res 2000;46:264-8.
129. Lijnen PJ, Petrov VV, Fagard RH. Induction of cardiac fibrosis by transforming growth factor-beta(1). Mol Genet Metab 2000;71:418-35.
130. Brilla CG, Zhou G, Matsubara L, Weber KT. Collagen metabolism in cultured rat cardiac fibroblasts: response to angiotensin II and aldosterone. J Mol Cell Cardiol 1994;26:809-20.
131. MacLellan WR, Schneider MD. Death by design. Programmed cell death in cardiovascular biology and disease. Circ Res 1997;81:137-44.
132. Eckardt L, Haverkamp W, Johna R et al. Arrhythmias in heart failure: current concepts of mechanisms and therapy. J Cardiovasc Electrophysiol 2000;11:106-17.