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(Circulation. 2007;116:2139-2147.)
© 2007 American Heart Association, Inc.

Molecular Cardiology

CD36 Expression Contributes to Age-Induced Cardiomyopathy in Mice

Debby P.Y. Koonen, PhD; Maria Febbraio, PhD; Sebastien Bonnet, PhD; Jayan Nagendran, MD; Martin E. Young, PhD; Evangelos D. Michelakis, MD; Jason R.B. Dyck, PhD

From the Cardiovascular Research Group (D.P.Y.K., J.R.B.D.) and the Vascular Biology Group (D.P.Y.K., S.B., J.N., E.D.M., J.R.B.D.), Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology (M.F.), Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio; and Baylor College of Medicine (M.E.Y.), Children’s Nutrition Research Center, Houston, Tex.

Correspondence to Dr Jason R.B. Dyck, 474 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. E-mail jason.dyck{at}ualberta.ca

Received May 10, 2007; accepted September 7, 2007.

Background— 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.

Methods and Results— 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.

Conclusions— 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.

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