LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia-reperfusion
LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia-reperfusion
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DOI：
10.1016/j.cardiores.2007.07.003
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发表时间：
2007-11-01
影响因子：
10.8
通讯作者：
Mehta, Jawahar L.
中科院分区：
文献类型：
--
作者：
Hu, Changping;Dandapat, Abhijit;Mehta, Jawahar L.
目的：慢性缺血与导致心肌重构的基因改变有关。活性氧（reactive oxygen species，ROS）的产生是心脏重塑的重要生化基础。一些研究表明，急性缺血触发重塑信号。我们研究了这样的假设，即有针对性地删除凝集素样氧化低密度脂蛋白受体（LOX-1）可能会抑制与心脏重塑相关的信号。方法与结果：我们在C57 BL/6（野生型小鼠）背景下产生LOX-1敲除（KO）小鼠，并使野生型和KO小鼠经受缺血-再灌注（I-R）。I-R后，野生型小鼠左心室收缩压和+/- dp/dt（max）显著降低，左心室舒张末期压升高，而LOX-1 KO小鼠的这种变化要小得多，表明LOX-1缺失后左心室功能得以保留。有证据表明，野生型小鼠I-R后存在明显的氧化应激（NADPH氧化酶表达、丙二醛和8-异前列腺素），LOX-1 KO小鼠的情况要少得多（P
Objective: Chronic ischemia is associated with alterations in genes that result in myocardial remodeling. An important biochemical basis of cardiac remodeling is generation of reactive oxygen species (ROS). A few studies have suggested that acute ischemia triggers signals for remodeling. We examined the hypothesis that targeted deletion of lectin-like oxidized-LDL receptor (LOX-1) may inhibit signals related to cardiac remodeling. Methods and results: We generated LOX-1 knockout (KO) mice on C57BL/6 (wild-type mice) background, and subjected wild-type and KO mice to ischemia-reperfusion (I-R). The wild-type mice developed a marked reduction in left ventricular systolic pressure and +/- dp/dt(max) and an increase in left ventricular end-diastolic pressure following I-R, and this change was much less in the LOX-1 KO mice, indicating preservation of left ventricular function with LOX-1 deletion. There was evidence for marked oxidative stress (NADPH oxidase expression, malondialdehyde and 8-isoprostane) following I-R in the wild-type mice, much less so in the LOX-1 KO mice (P