Cardiomyocyte apoptosis in acute and chronic conditions

Abstract

Myocytes can die by necrosis or by apoptosis and the characteristics of both kinds of cell death are so typical that a differentiation can be made by histological and molecular-biological methods using electron microscopy, dUTP labeling with fluorescence or peroxidase staining (TUNEL) and the DNA laddering method. However, the problem of quantification of apoptotic cells has not been completely solved because of lack of standardization as well as uncritical use and interpretation of the TUNEL method. Equally, quantification of apoptotic cells is not optimal until now because of three reasons: methodological (overinterpretation of results, no differentiation between myocytes and non-myocytes), experimental (global or regional acute ischemia, chronic conditions such as heart failure or hibernating myocardium), and interpretation (unknown time period for the completion of apoptosis). This problem is reflected in the large differences in incidence of apoptosis reported. Our own data show that in dog myocardium made globally ischemic for 90 min, 8% of the myocytes showed a positive staining for apoptosis (TUNEL method) after 6 h of reperfusion. Despite these results the question of reperfusion injury and the influence of apoptosis still remains open, because it can not be excluded until now that the apoptotic process is initiated during the ischemic period. Studies in hibernating myocardium and chronic heart failure show a similar situation, because of a wide variation of numbers of apoptotic cells and the limited possibility to investigate human tissue. There is no doubt that apoptosis plays an important role in chronic pathophysiological situations such as heart failure and hibernating myocardium but the importance of apoptosis in the acute situation of ischemia/reperfusion still has to be clarified.

Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension

“…In this sequence, we assessed the LV myocardial apoptosis, and found increased rates of apoptosis both in MCT-4 and MCT-6. Although there is some controversy about the role of apoptosis in chronic heart failure [1,7,22], this results suggest that it might be another possible mechanism involved in early events of LV dysfunction.…”

Anti-hypoxic effect of ginsenoside Rbl on neonatal rat cardiomyocytes is mediated through the specific activation of glucose transporter-4 ex vivo

“…Ischemia and hypoxia, if not corrected, can lead to cardiomyocyte "hibernation," apoptosis and even necrosis. Hibernating myocardium, an adaptive response to ischemia and/or metabolic imbalance [1][2][3][4][5][6] , may result in characteristic ultrastructural changes in cardiomyocytes, such as myolysis and subsequent glycogen accumulation in the myolytic areas [3][4][5][6] . Although it is reversible, cardiomyocyte "hibernation" and apoptosis will damage heart function to an extreme extent.…”

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

“…Caspase 8 plays a role in CD95-and tumor necrosis factor-induced cell death (24). Apoptosis has been associated with heart damage in numerous diseases, such as viral infection, myocardial infarction, diabetes, and regression of hypertrophy (37,38). Apoptosis assessed by the TUNEL method has been shown in CCC, and myocardial cell loss by apoptosis may contribute to heart failure (39).…”