The Role Of LOX-1 And Its Mechanism In Cardiomyocyte Apoptosis Following Coronary Microembolization

Background:Cardiomyocyte apoptosis by coronary microembolization (CME) contributes to myocardial dysfunction, in which the mitochondrial pathway and death receptor pathway were activated. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein involved in apoptosis. Whether or not it involves in the activation of the mitochondria pathway and death receptor pathway following CME is currently unknown. The study was designed to explore the role of LOX-1 and its mechanism in the activation of these two major apoptotic pathways following CME.Methods:Twenty swine were randomized into 4 groups (n=5 for per group):Sham; CME; LOX-1 siRNA; Control siRNA. Microspheres (diameter 42pm) were injected into the left anterior descending artery of swine to establish CME models, while swine in the sham group received normal saline instead. Swine in the LOX-1 siRNA group and Control siRNA group were treated with LOX-1 siRNA and Control siRNA intracoronarily, respectively 24 h prior to CME. Twelve hours after operation, cardiac function, serum c-troponin I level, microinfarct and apoptotic index were examined. The levels of LOX-1, Bcl-2, Bax, cytochrome c, as well as cleaved caspase-9/-8/-3 of myocardial tissue were detected.Results:As compared with the sham group, myocardial dysfunction, enhanced serum c-troponin I, microinfarct and apoptosis were induced in the CME group. Moreover, CME induced increased expression of LOX-1, Bax, cytochrome c, cleaved caspase-9/-8/-3, as well as decreased Bcl-2 expression. LOX-1 siRNA reversed these effects by CME except cleaved caspase-8 expression, while the control siRNA had no effect.Conclusion:CME induces cardiomyocyte apoptosis via the death receptor pathway and the LOX-1-dependent mitochondrial pathway. LOX-1 may serve as a new target for the prevention and treatment of cardiac impairment by CME.