CD36 and interacting stresses in cardiomyopathy

Cardiac patients often are obese/diabetic and have hypertension, but these complications are mainly studied separately. We investigated in mice whether 1) mechanophysical stress and metabolic stress interact in the development of cardiac dysfunction and remodeling, and 2) ablation of the fatty‐acid transporter CD36 relieves this interaction. Wildtype (WT) and CD36−/− mice received chow or western‐type diet (WTD) for 10 weeks, and then underwent a sham surgery or transverse aortic constriction (TAC). After 6 weeks continuation of the diet, cardiac function and composition were assessed. WTD or CD36 ablation worsened the outcome of TAC, i.e. 1) reduced fractional shortening, 2) increased left ventricle end systolic diameter, and 3) increased left ventricle weight. In mice receiving WTD, ablation of CD36 protected against the cardiac functional and structural changes induced by TAC. Cardiac lipid concentrations increased in WT mice receiving WTD, decreased in CD36−/−, and remained unchanged in CD36−/− receiving WTD. In conclusion, cardiac dysfunction and remodeling worsen when the heart is exposed to both mechanophysical and metabolic stress. CD36 ablation protects against the metabolic stress resulting from a WTD. Thus, metabolic conditions are a critical factor for the compromised heart and provide new targets for metabolic manipulation in cardioprotection. Funding DFN Grant 2006.00.044.