Cell death in the pathogenesis of heart disease: mechanisms and significance

• Published in: Annual review of physiology Vol. 72; no. 1; pp. 19 - 44
• Main Authors: Whelan, Russell S, Kaplinskiy, Vladimir, Kitsis, Richard N
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews, Inc 01-01-2010
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Autophagy - drug effects; Autophagy - physiology; Cardiovascular disease; Cell Death - drug effects; Cell Death - physiology; Cells; Heart Diseases - drug therapy; Heart Diseases - pathology; Heart Failure - pathology; Humans; Mitochondria, Heart - physiology; Morphology; Myocardial Infarction - pathology; Necrosis - pathology; Pathogenesis; Signal Transduction - drug effects; Signal Transduction - physiology
• ISSN: 0066-4278; 1545-1585
• DOI: 10.1146/annurev.physiol.010908.163111

Cell death was once viewed as unregulated. It is now clear that at least a portion of cell death is a regulated cell suicide process. This type of death can exhibit multiple morphologies. One of these, apoptosis, has long been recognized to be actively mediated, and many of its underlying mechanisms have been elucidated. Moreover, necrosis, the traditional example of unregulated cell death, is also regulated in some instances. Autophagy is usually a survival mechanism but can occur in association with cell death. Little is known, however, about how autophagic cells die. Apoptosis, necrosis, and autophagy occur in cardiac myocytes during myocardial infarction, ischemia/reperfusion, and heart failure. Pharmacological and genetic inhibition of apoptosis and necrosis lessens infarct size and improves cardiac function in these disorders. The roles of autophagy in ischemia/reperfusion and heart failure are unresolved. A better understanding of these processes and their interrelationships may allow for the development of novel therapies for the major heart syndromes.