Abstract
Heart failure (HF) is a major problem worldwide, but its pathogenesis remains unclear. Apoptosis or programmed cell death is thought to play a crucial role in its progression. While primarily thought to be a method for cardiomyocyte loss, provocative newer data suggest that the apoptotic cell is not inevitably committed to death. Apoptosis might be one of the meta-stable transition states, like the hibernating myocardium, that may be reversible with appropriate therapy. The cell with activated apoptotic machinery is likely to contribute to reversible systolic dysfunction while awaiting its ultimate fate. We will briefly review some of the data to support such a concept. If proven correct, this may change our future preventive and therapeutic strategies. Methods to reverse apoptosis, thus might help restore systolic function and reverse remodeling or even prevent progression of heart failure.
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References
American Heart Association: Heart Disease and Stroke Statistics (2007) Circulation 115:e69–e171
Narula J, Young JB (2005) Pathogenesis of heart failure: the penultimate survival instinct. Heart Fail Clin 1:ix–x
Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E, Sonnenblick E (1995) The cellular basis of dilated cardiomyopathy in humans. J Mol Cell Cardiol 27:291–305
Pouleur HG, Konstam MA, Udelson JE, Rousseau MF (1993) Changes in ventricular volume, wall thickness and wall stress during progression of left ventricular dysfunction. The SOLVD investigators. J Am Coll Cardiol 22:43A–48A
Chandrashekhar Y, Narula J (2003) Death hath a thousand doors to let out life. Circ Res 92:710–714
Wencker D, Chandra M, Nguyen K, Miao W, Garantziotis S, Factor SM et al (2003) A mechanistic role for cardiac myocyte apoptosis in heart failure. J Clin Invest 111:1497–1504
Hayakawa K, Takemura G, Kanoh M, LiY, Koda M, Kawase Y et al (2003) Inhibition of granulation tissue cell apoptosis during the subacute stage of myocardial infarction improves cardiac remodelling and dysfunctionat the chronic stage. Circulation 108:104–109
Chandrashekhar Y, Sen S, Anway R, Shuros A, Anand I (2004) Long-term caspase inhibition ameliorates apoptosis, reduces myocardial troponin-I cleavage, protects left ventricular function, and attenuates remodeling in rats with myocardial infarction. J Am Coll Cardiol 43:295–301
Narula J, Haider N, Virmani R et al (1996) Apoptosis in myocytes in end-stage heart failure. N Engl J Med 335:1182–1189
Olivetti G, Abbi R, Quaini F et al (1997) Apoptosis in the failing human heart. N Eng J Med 336:1131–1141
Garg S, Narula J, Chandrashekhar Y (2005) Apoptosis and heart failure: clinical relevance and therapeutic target. J Mol Cell Cardiol 38:73–79
Anversa P (2000) Myocyte death in the pathological heart. Circ Res 86:121–124
Narula J, Arbustini E, Chandrashekhar Y, Schwaiger M (2001) Apoptosis and the systolic dysfunction in congestive heart failure: story of apoptosis interruptus and Zombie myocytes. Cardiol Clin 19:113–126
Narula J, Pandey P, Arbustini E et al (1999) Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy. Proc Natl Acad Sci USA 96:8144–8149
Reed JC, Paternostro G (1999) Postmitochondrial regulation of apoptosis during heart failure. Proc Natl Acad Sci USA 996:7614–7616
Narula J, Haider N, Arbustini E, Chandrashekhar Y (2006) Mechanisms of disease: apoptosis in heart failure—seeing hope in death. Nat Clin Pract Cardiovasc Med 3:681–688
Haider N, Narula N, Narula J (2002) Apoptosis in heart failure represents programmed cell survival, not death, of cardiomyocytes and likelihood of reverse remodelling. J Card Fail 8(6 Suppl):S512–S517
Kanoh M. Takemura G. Miaao J. Hayakawa Y, Aoyama T, Nishigaki K, Noda T, Fujiwara T, Fukuda K, Mitatoguchi S, Fujiwara H (1999) Significance of myocytes with DNA in situ nick-end labeling (TUNEL) in hearts with dilated cardiomyopathy: not apoptosis but DNA repair. Circulation 99:2757–2764
Morissette MR, Rosenzweig A (2005) Targeting survival signaling in heart failure. Curr Opin Pharmacol 5:165–170
Narula N, Narula J, Zhang PJ et al (2005) Is the myofibrillarlytic myocyte a forme fruste apoptotic myocyte? Ann Thorac Surg 79:1333–1337
Communal C, Sumandea M, de Tombe P, Narula J, Solaro RJ, Hajjar RJ (2002) Functional consequences of caspase activation in cardiac myocytes. Proc Natl Acad Sci USA 99:6252–6256
Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185:1481–1486
Grazette LP, Boecker W, Matsui T et al (2004) Inhibition of ErbB2 causes mitochondrial dysfunction in cardio-myocytes. Implications for herceptin-induced cardiomyopathy. J Am Coll Cardiol 44:2231–2238
Crone SA, Zhao YY, Fan L et al (2002) ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med 8:459–465
Matsui T, Tao J, del Monte F et al (2001) Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation 104:330–335
Bartling B, Milting H, Schumann H et al (1999) Myocardial gene expression of regulators of myocyte apoptosis and myocyte calcium homeostasis during hemodynamic unloading by ventricular assist devices in patients with end-stage heart failure. Circulation 100:216–223
Arbustini E, Norbini P, Narula J et al (2001) Apoptosis in heart failure: abrogation of cytochrome c release after ventricular unloading by LVAD (abstr). Med Pathol
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Masri, C., Chandrashekhar, Y. Apoptosis: a potentially reversible, meta-stable state of the heart. Heart Fail Rev 13, 175–179 (2008). https://doi.org/10.1007/s10741-007-9069-3
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DOI: https://doi.org/10.1007/s10741-007-9069-3