Understanding the impact of mitochondrial defects in cardiovascular disease: a review.

OBJECTIVE: Defects in mitochondrial structure and function have been found in association with cardiovascular diseases such as dilated and hypertrophic cardiomyopathy, cardiac conduction defects and sudden death, ischemic and alcoholic cardiomyopathy, and myocarditis. A genetic basis has been established for some mitochondrial abnormalities (eg, mitochondrial DNA changes leading to oxidative phosphorylation dysfunction, fatty acid beta-oxidation (FAO) defects resulting from specific nuclear mutations) whereas other abnormalities appear to be due to a more sporadic or environmental cardiotoxic insult or have not yet been characterized.

METHODS: This article reviews mitochondrial abnormalities in structure or function reported in cardiac diseases highlighting information about their potential etiology, significance in cardiac pathogenesis, and diagnostic and therapeutic options available to the clinician. We also provide a brief background concerning mitochondrial biogenesis and bioenergetic pathways in cardiac growth, development, and aging.

CONCLUSIONS: Although aberrations in bioenergetic functioning of mitochondria appear to be most often related to cardiac dysfunction, the primary defect(s) causing bioenergetic dysfunction may reside in a nonbioenergetic pathway (eg, signaling between mitochondria and nucleus) or in overall mitochondrial biogenesis or degradation pathways.