Pressure overload leads to coronary plaque formation, progression, and myocardial events in ApoE–/– mice

Hypercholesterolemia and hypertension are two major risk factors for coronary artery diseases, which remain the major cause of mortality in the industrialized world. Current animal models of atherosclerosis do not recapitulate coronary plaque disruption, thrombosis and myocardial infarction occurring in human. Recently, we demonstrated that exposure of the heart to high pressure, by transverse aortic constriction (TAC), induced coronary lesions in ApoE-/- mice on chow diet. The aim of this study was to characterize the magnitude and location of coronary lesions in ApoE-/- mice post-TAC, and to assess the susceptibility of coronary plaque to disruption, leading to myocardial events. Here we describe a reliable pathological condition in mice characterized by the development of coronary lesions and its progression leading to myocardial infarction, which better recapitulate human disease. Following TAC surgery, about 90% of ApoE-/- mice develop coronary lesions, especially in the left anterior descending artery, with 59% of the mice manifesting different magnitude of LAD stenosis. Myocardial events, identified in 74% of the mice, were mainly due to coronary plaque thrombosis and occlusion. That TAC induces the development and progression of coronary lesions in ApoE-/- mice leading to myocardial events represents a novel and important tool to investigate the development of coronary lesions and its sequelae in a setting that better resemble human conditions.