Activation of Peroxisome Proliferator–Activated Receptor-α Protects the Heart From Ischemia/Reperfusion Injury

Background— Peroxisome proliferator–activated receptor-α (PPAR-α) is expressed in the heart and regulates genes involved in myocardial fatty acid oxidation (FAO). The role of PPAR-α in acute ischemia/reperfusion myocardial injury remains unclear. Methods and Results— The coronary arteries of male mice were ligated for 30 minutes. After reperfusion for 24 hours, ischemic and infarct sizes were determined. A highly selective and potent PPAR-α agonist, GW7647, was administered by mouth for 2 days, and the third dose was given 1 hour before ischemia. GW7647 at 1 and 3 mg · kg −1 · d −1 reduced infarct size by 28% and 35%, respectively ( P Conclusions— Activation of PPAR-α protected the heart from reperfusion injury. This cardioprotection might be mediated through metabolic and antiinflammatory mechanisms. This novel effect of the PPAR-α agonist could provide an added benefit to patients treated with PPAR-α activators for dyslipidemia.