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Background— Several clinical studies have demonstrated that levels of adiponectin are significantly reduced in patients with type 2 diabetes and that adiponectin levels are inversely related to the risk of myocardial ischemia. The present study was designed to determine the mechanism by which adiponectin exerts its protective effects against myocardial ischemia/reperfusion.

Methods and Results— Adiponectin^−/− or wild-type mice were subjected to 30 minutes of myocardial ischemia followed by 3 hours or 24 hours (infarct size and cardiac function) of reperfusion. Myocardial infarct size and apoptosis, production of peroxynitrite, nitric oxide (NO) and superoxide, and inducible NO synthase (iNOS) and gp91^phox protein expression were compared. Myocardial apoptosis and infarct size were markedly enhanced in adiponectin^−/− mice (P<0.01). Formation of NO, superoxide, and their cytotoxic reaction product …