标题：Cardiac-generated leukotriene B4 promotes pathogenesis of myocardial ischemia-reperfusion injury
作者：Zuo L.; Liu Y.; Li S.; Wei D.; Qiu H.
作者机构：[Zuo, L] Department of Cardiology, Yantaishan Hospital, Yantai, China, Shandong University, Jinan, China;[ Liu, Y] People's Hospital of Zhangqiu City, 更多
通讯作者地址：Qiu, H.; Department of Internal Medicine, University of California, Davis, 2425 Stockton Blvd, Sacramento, CA 95817, United States; 电子邮件: hong.qiu 更多
来源：Experimental and Clinical Cardiology
关键词：Apoptosis; Leukotriene; Myocardial ischemia/reperfusion injury
摘要：This study investigates the role of cardiac generated leukotriene B4 (LTB4) in ischemia/reperfusion induced myocardial injury. Increased expression of key enzymes in LTB4 biosynthetic pathway, specifically 5-lipoxigenase and leukotriene A4 hydrolase, was demonstrated in mouse heart tissue after ischemia/reperfusion for 1-3 days. In vitro experiment demonstrated that LTB4 can directly induce apoptosis in cardiac myocytes. This effect involves the down-regulation of anti-apoptotic gene BcL-2. In addition, LTB4 also enhanced the expression of MMP-2 in cardiac myocytes. Treatment of MI mice with 5-lipoxygenase inhibitor Zileuton effectively inhibited ischemia/reperfusion- induced LTB4 generation, resulting in the reduction in cardiac apoptosis and MMP-2 production, and improvement of cardiac function. Further understanding of the mechanisms underlying LTB4 induced cardiac injury may be of significant value in designing new therapeutic strategies to prevent aberrant cell loss following MI and subsequent progression to heart failure.