Apoptosis: basic mechanisms and implications for cardiovascular disease.

Since Kerr et al1 in 1972 coined the term “apoptosis” for a morphologically distinct mode of cell death, this concept of cell suicide has gained increasing interest in cytology and pathology. In terms of tissue kinetics, apoptosis may be considered a mechanism that counterbalances the effect of cell proliferation by mitotic division. In fact, deregulated apoptosis has been implicated as a fundamental pathogenetic mechanism in a variety of human diseases. Excessive apoptotic cell death may cause organ atrophy and organ failure, as suggested for neurodegenerative diseases and viral hepatitis. On the other hand, inefficient elimination of malignant, autoreactive, infected, or redundant cells may lead to the development of neoplasia, autoimmunity, viral persistence, and congenital malformations. Further interest in apoptosis has arisen from the recent elucidation of effector and regulatory mechanisms with the aid of molecular biology, genetics of lower organisms, and genetic modification of the mouse. However, only recently, compelling evidence has accumulated indicating that apoptotic cell death may also play a critical role in a variety of cardiovascular diseases, including myocardial infarction, heart failure, and atherosclerosis. Apoptosis can be differentiated from other forms of cell death that occur in response to toxins, physical stimuli, and ischemia. Although not widely used, this form of cell death was termed “accidental cell death” in the pathology literature.2 In contrast to apoptosis, accidental cell death does not involve suicide mechanisms and is not energy dependent. In the case of accidental cell death induced by ischemia, depletion of intracellular ATP stores, swelling, and disruption of the cell membrane, leading to liberation of cytoplasmic contents into the extracellular space, are prominent features (Figure 1⇓). This specific form of accidental cell death is also referred to as “oncosis.” The term “necrosis,” often used to describe cell death other than apoptotic cell death, is …