Basic mechanisms in apoptosis and heart failure

The syndrome of heart failure may arise from different causes but there are features that are common to all: myocardial fibrosis, desensitization of b-adrenergic receptor signalling, excitation-contraction uncoupling, myosin isoform switch, altered energy utilization and ‘‘cell loss’’. These unifying features imply that the molecular pathways that underpin them are activated in most, if not all, instances of heart failure. Good response to therapy such as angiotensin receptor or b-adrenergic receptor blockade, is also not selective to only specific causes of heart failure. Thus many molecular mechanisms now form important targets in the heart failure drug discovery pipeline. The best-understood form of "cell loss" in the myocardium is APOPTOSIS. Both evolutionarily conserved pathways of apoptosis: extrinsic and intrinsic, are activated in heart failure. Apoptotic cell death involves the recruitment of death activating complexes whose formation is dependent on specific protein motifs called death domain motifs. Apoptotic cell death also characteristically requires the activation of caspases that selectively cleave proteins, eventually leading to cell disassembly. This review covers the basic mechanisms involved in apoptosis and heart failure. Heart Metab. 2010;47:5–8.