Cardioprotection from ischemia/reperfusion injury is impaired in mice with coronary atherosclerosis or insulin resistance, but this is overcome by a direct chemical activator of PI3Kalpha

Background and Aims: In patients with coronary artery disease (CAD), morbidity and mortality from ST-elevation myocardial infarction (STEMI) remain high. Cardioprotective strategies such as Remote Ischemic Conditioning (RIC) are highly effective in animal models but have disappointed in clinical trials. This disconnect may partly be because experiments are typically conducted in mice without CAD. Double-knockout Scarb1;Ldlr (DKO) mice develop coronary atherosclerotic plaques when fed a high-fat diet (HFD).