Internucleosomal DNA Fragmentation in Apoptotic Myocytes

Abstract

An estimated 400 000 or more new cases of cardiovascular disease are diagnosed annually in the US, accounting for the majority of morbidity and mortality from heart disease (1). Coronary artery stenosis accounts for many of these cases because of subsequent necrosis of myocardial tissues. Increasing evidence now suggests that the central dogma of myocardial infarction pathophysiology, cell death from necrosis, should now concomitantly include discussion of apoptosis, or programed cell death (1)(2)(3)(4)(5)(6)(7). Necrosis of myocytes results from physiological imbalances caused by lack of oxygenated blood supply to these cells. This process of cell death is characterized by depletion of ATP concentrations, intracellular damage to organelles, cell swelling or hypertrophy, rupture of cell membranes, and induction of an acute inflammatory response. Quite distinctive from necrosis is a second method of cell death, apoptosis, which is a highly regulated and systematic form of programed cell death (8)(9). This energy-dependent process involves loss of cell-to-cell contact, cell shrinkage, condensation of nuclear chromatin, and eventual endonucleolytic fragmentation of genomic DNA. Apoptosis functions as a regulator of biological homeostasis and is often associated with cells that are progressing through the cell cycle. Thus, until recently, investigators had believed that this mechanism of programed cell death was not associated with terminally differentiated adult cells such as myocytes, neural cells, or hepatocytes. Recent studies, however, have shown that myocardial cell apoptosis can be induced by a variety of insults, including hypoxia, acute ischemia–reperfusion, myocardial infarction, cardiomyopathy–end-stage heart failure, and myocardial pressure stretch (1)(2)(3)(4)(5)(6)(7). Subsequent to various pathological stresses, the myocardium responds to bodily demands for increased cardiac output through a variety of compensatory physiological mechanisms, e.g., myocyte hypertrophy, increased …