Caligiuri G, Levy B, Pernow J, Thorén P, Hansson G K
Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, SE-17176 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6920-4. doi: 10.1073/pnas.96.12.6920.
Myocardial infarction is linked to atherosclerosis, yet the sequence leading from silent coronary atherosclerosis to acute myocardial infarction has remained unclear. Here we show that hypercholesterolemic apolipoprotein E-/- low density lipoprotein receptor-/- mice develop not only coronary atherosclerosis but also myocardial infarction. Exposure of mice to mental stress or hypoxia led to acute ischemia, which, in a large proportion of the mice, was followed by electrocardiographic changes, leakage of troponin T, and loss of dehydrogenase from the myocardium, all indicative of acute myocardial infarction. Apoptotic death of cardiomyocytes was followed by inflammation and fibrosis in the heart. All these pathological changes could be prevented by a blocker of the endothelin type A receptor. Thus, stress elicits myocardial infarction through endothelin receptor signaling in coronary atherosclerosis caused by hypercholesterolemia.
心肌梗死与动脉粥样硬化相关,但从无症状性冠状动脉粥样硬化发展到急性心肌梗死的过程仍不清楚。在此,我们表明,高胆固醇血症的载脂蛋白E基因敲除/低密度脂蛋白受体基因敲除小鼠不仅会发生冠状动脉粥样硬化,还会发生心肌梗死。将小鼠暴露于精神应激或低氧环境会导致急性缺血,在很大一部分小鼠中,随后会出现心电图改变、肌钙蛋白T泄漏以及心肌中脱氢酶的丧失,所有这些都表明发生了急性心肌梗死。心肌细胞凋亡性死亡之后是心脏的炎症和纤维化。所有这些病理变化都可以通过A型内皮素受体阻滞剂来预防。因此,在高胆固醇血症引起的冠状动脉粥样硬化中,应激通过内皮素受体信号传导引发心肌梗死。