Myocardial infarction mediated by endothelin receptor signaling in hypercholesterolemic mice

Myocardial infarction is linked to atherosclerosis, yet the sequence leadin g from silent coronary atherosclerosis to acute myocardial infarction has r emained unclear. Here we show that hypercholesterolemic apolipoprotein E-/- low density lipoprotein receptor(-/-) mice develop not only coronary ather osclerosis but also myocardial infarction, Exposure of mice to mental stres s or hypoxia led to acute ischemia, which, in a large proportion of the mic e, was followed by electrocardiographic changes, leakage of troponin T, and loss of dehydrogenase from the myocardium, all indicative of acute myocard ial infarction, Apoptotic death of cardiomyocytes was followed by inflammat ion and fibrosis in the heart. All these pathological changes could be prev ented by a blocker of the endothelin type A receptor. Thus, stress elicits myocardial infarction through endothelin receptor signaling in coronary ath erosclerosis caused by hypercholesterolemia.