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Apoptosis: a pivotal event or an epiphenomenon in the pathophysiology of heart failure?
  1. DAVID MARSHALL,
  2. MICHAEL N SACK
  1. Hatter Institute for Cardiology Research
  2. UCT Medical School
  3. Cape Town 7925
  4. South Africa
  5. sack@samiot.uct.ac.za

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Apoptosis, or programmed cell death, is an evolutionary conserved genetically programmed process by which multicellular organisms regulate cell numbers. It is critical in development and in tissue homeostasis. Unlike necrosis, the process is active, energy requiring and precisely regulated.

Apoptosis in cardiac development and disease

Cardiac myocytes are by and large terminally differentiated and have a limited capacity for self renewal. It would therefore seem that loss of a significant number of cardiomyocytes would have lasting adverse consequences. Apoptosis is, however, integral to normal cardiac development and is also important in the morphogenesis of the conducting system. This can be illustrated by accessory pathway mediated arrhythmias caused by inadequate removal of loop short circuit cells by apoptosis. Apoptotic cardiomyocytes have also been identified in subjects with ischaemic heart disease and myocarditis. Moreover, evidence exists to show that apoptosis occurs in “end stage” heart failure. The relevance of this process in the overall pathophysiology and progression of heart failure is, however, still controversial. We hope to convey the current understanding of apoptosis with respect to its prevalence and its putative impact on chronic stable cardiomyopathy. We will also discuss the theoretical implications of blocking the apoptotic programme in the management of heart failure.

Apoptosis and the pathophysiology of heart failure

Quantifying the number of apoptotic cells has been fraught with difficulty and the merits of the various analytical techniques for determining apoptosis are vigorously debated.1 , …

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