Myocyte apoptosis in heart failure

Abstract

Human heart failure is preceded by a process termed cardiac remodeling in which heart chambers progressively enlarge and contractile function deteriorates. Programmed cell death (apoptosis) of cardiac muscle cells has been identified as an essential process in the progression to heart failure. The execution of the apoptotic program entails complex interactions between and execution of multiple molecular subprograms. Unlike necrosis, apoptosis is an orderly regulated process and, by inference, a logical therapeutic target if intervention occurs at an early stage. To identify potential therapeutic targets, it is imperative to have a full understanding of the apoptotic pathways that are functional in the cardiac muscle. Accordingly, the present review summarizes the apoptotic pathways operative in cardiac muscle and discusses therapeutic options related to apoptosis for the future treatment of human heart failure.

Myocardial apoptosis associated with the expression of proinflammatory cytokines during the course of myocardial infarction

“…The difference in the proportions of cardiomyocyte apoptosis have been reported in the previous studies, 10,[29][30][31] and the difference between the studies might have been due to differences in the tissue samples taken or the method used for analysis of myocardial tissue. 7,32 However, a previous literature by van Empel et al reviewed a prevalence of cardiomyocyte apoptosis ranging from 0.12 to 0.70% in myocardial biopsy specimens obtained from patients with NYHA classes III-IV heart failure, 30,[33][34][35][36][37][38][39][40] which was similar to the figure obtained in the present study. Therefore, the variation in the prevalence of cardiomyocyte apoptosis between the reported studies may not have been due to differences in the myocardial tissue samples used for analysis.…”

Deficiency of Capn4 Gene Inhibits Nuclear Factor-κB (NF-κB) Protein Signaling/Inflammation and Reduces Remodeling after Myocardial Infarction

“…Cardiomyocyte drop-out due to apoptosis is a defining cellular event related to ventricular remodeling and development of heart failure (37,38). Continuing cardiomyocyte apoptosis increases infarct expansion, which occurs after MI, leading to compensative and maladaptive hypertrophy, and loss of cardiomyocytes is replaced by fibrosis as cardiomyocytes are unable to proliferate and the generation of new cardiomyocytes is largely limited (37).…”

Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited

“…However, the relevance of apoptosis in DOX-induced dilated cardiomyopathy is often questioned as the amount of apoptosis in biopsies from patients or from heart transplants following DCM is low compared to necrotic cell death [18]. A suggested reason for the low amount of apoptosis detected in DCM is that apoptosis gradually evolves over time, initiating a slow mechanism of cardiomyocyte hypertrophy over years to replace cardiomyocyte loss [19].…”

“…Apoptosis then may then occur gradually over time in response to somatic stimuli resulting in a continuously evolving compensatory cardiomyocyte hypertrophy and extracellular matrix adaptation to replace cell loss [19].…”