Submitted to: Circulation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/7/2007
Publication Date: 10/22/2007
Citation: Koonen, D.P., Febbraio, M., Bonnet, S., Nagendran, J., Young, M.E., Michelakis, E.D., Dyck, J.R. 2007. CD36 expression contributes to age induced cardiomyopathy in mice. Circulation. 116(19):2139-2147. Interpretive Summary: Elderly individuals have an increased risk of heart disease. An excess of fatty acids (beyond the ability to burn them as a fuel) has been associated with heart disease. This study investigated whether age-related changes in the ability of the heart to take up fatty acids from the circulation contribute toward increased heart disease with aging. CD36 promoted the uptake of fatty acids. CD36 levels were found to be increased in the heart with age. Removal of CD36 from the heart improved heart function in elderly animals. These data suggest that increased CD36 levels in the aging heart might contribute toward heart disease.
Technical Abstract: Cardiac remodeling and impaired cardiac performance in the elderly significantly increase the risk of developing heart disease. Although vascular abnormalities associated with aging contribute to the age-related decline in cardiac function, myocardium-specific events may also be involved. We show that intramyocardial lipid accumulation, as well as a reduction in both fatty acid and glucose oxidation and a subsequent deterioration in cardiac ATP supply, also occurs in aged mice. Consistent with an energetically compromised heart, hearts from aged mice display depressed myocardial performance and cardiac hypertrophy. Associated with this is a dramatic increase in the fatty acid transport protein CD36 in aged hearts compared with young hearts, which suggests that CD36 is a mediator of these multiple metabolic, functional, and structural alterations in the aged heart. In accordance with this, hearts from aged CD36-deficient mice have lower levels of intramyocardial lipids, demonstrate improved mitochondria-derived ATP production, have significantly enhanced function compared with aged wild-type mice, and have a blunted hypertrophic response. These findings provide evidence that CD36 mediates an age-induced cardiomyopathy in mice and suggest that inhibition of CD36 may be an approach for the treatment of the detrimental age-related effects on cardiac performance.