Apoptosis in heart failure

The finding that cardiomyocyte apoptosis occurs in the end stage human heart indicates that apoptosis may contribute to heart failure in a variety of situations.5 6 Aging is associated with

Table 30.1 Characteristic features of apoptosis versus necrosis

Apoptosis

Necrosis

Condensation/clumping of nuclear chromatin

Loss of cell-cell contact, cell shrinkage, and fragmentation, with formation of membrane bound processes and vesicles containing fragments of nuclear material or organelles

Adjacent cells phagocytose the end product, the apoptotic body

Minimal disruption of cell membranes or release of lysosomal enzymes, with consequently little inflammatory reaction

Organelle structure and function maintained until late into the process

Nuclear chromatin non-specifically

Cell volume increases

Cell membrane integrity lost early, release of lysosomal enzymes and subsequent inflammation

Organelle structure and function lost early myocardial cell loss, and cardiomyocyte apoptosis may be the mechanism of the gradual deterioration in cardiac function. In humans undergoing transplantation, apoptosis can be observed,6 with some studies suggesting higher levels in ischae-mic versus idiopathic dilated cardiomyopathy.5 The transition from compensated to decompensated hypertrophy is also associated with myocyte apoptosis in animals,7 and high levels of apoptosis are seen in arrhythmogenic right ventricular dyspla-sia, a condition characterised by myocardial replacement with fibrofatty material. Finally, there is increasing evidence that toxic cardiomyopathies, such as that induced by doxorubicin (Adriamycin), are associated with cardiomyocyte apoptosis.

Although the evidence that apoptosis promotes heart failure is persuasive, the present problem is defining by what extent. Vastly different rates of apoptosis have been reported in both human and animal heart failure, with rates of up to 35.5%.5 While these death rates may be seen only in very localised areas, given that apoptosis takes less than 24 hours to complete, such rates would result in rapid involution of the heart. More recently, rates of < 0.5% have been consistently reported in end stage heart failure, which make far more physiological sense. In addition, in end stage heart failure necrosis is still (up to seven times) more frequent than apoptosis.

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