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Cardiomyocyte Apoptosis in Experimental Health Failure

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Abstract

Heart failure is characterized by progressive worsening of left ventricular (LV) function over time. The mechanism(s) responsible for this hemodynamic deterioration are not known. It is often assumed, but by no means established, that progressive LV dysfunction results largely from ongoing loss of functional cardiac units. If ongoing myocyte loss occurs during the course of evolving heart failure and can indeed account for the progressive deterioration of LV dysfunction, then the identification of factors responsible for this loss of muscle mass can potentially lead to novel therapeutic modalities aimed at preventing the transition toward intractable heart failure. Recent studies in experimental animals have shown that cardiac myocyte loss through apoptosis, or programmed cell death, occurs 1) following myocardial infarction, 2) in the presence of cardiac hypertrophy, 3) in the aging heart, and 4) in the setting of chronic heart failure. The observation of myocyte apoptosis in experimental animal models of heart failure has since been confirmed in the failed human heart. Considerable work has also been accomplished, and credible concepts advanced, in an attempt to uncover the physiological and molecular triggers of myocyte apoptosis in heart failure. While, at present, one can comfortably accept the existence of the phenomenon of myocyte apoptosis in the failing heart, two integral questions remain essentially unanswered. First, what pathophysiological factors(s), inherent to heart failure, trigger myocyte apoptosis? Second, how important is myocyte apoptosis in the progression of LV dysfunction and the transition to overt failure? The present article will summarize our current knowledge of myocyte apoptosis based largely on data available from animal models of myocardial infarction, hypertrophy, and failure.

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  1. Hani N. Sabbah
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  2. Victor G. Sharov
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  3. Sidney Goldstein
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Sabbah, H.N., Sharov, V.G. & Goldstein, S. Cardiomyocyte Apoptosis in Experimental Health Failure. Heart Fail Rev 3, 35–43 (1998). https://doi.org/10.1023/A:1009702513648

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