Innate immunity in Myocardial Ischemia

描述（由申请人提供）：心肌缺血再灌注（MI/R）是血管手术和心肌梗死的常见临床问题。补体激活在与心肌梗死/R相关的局部和可能的远程组织损伤中起重要作用。我们实验室最近的证据表明，体内封锁甘露糖结合凝集素（MBL）可以阻止补体的沉积和激活，从而显著减少MI/R后的损伤和炎症基因表达。利用缺乏C1q或MBL或两者下游效应蛋白的小鼠，我们建议确定实验性MI/R后导致组织破坏的事件。在本提案中，我们将研究MI/R后MBL与C1q（即凝集素与经典途径）的作用。我们假设MI/R后的不可逆心脏损伤依赖于MBL和凝集素补体途径的激活。具体目的如下：1)表征mbl依赖性补体激活在MI/R损伤起始中的作用，并进一步评估C1q在MI/R中的作用；2)确定心肌梗死/再灌注后mbl依赖性损伤的机制。

DESCRIPTION (provided by applicant): Myocardial ischemia-reperfusion (MI/R) is a common clinical problem in the settings of vascular surgery and myocardial infarction. Complement activation plays an important role in local, and likely remote, tissue injury associated with MI/R. Recent evidence from our laboratory shows that blockade of mannose binding lectin (MBL) in vivo prevents deposition and activation of complement resulting in significantly reduced injury and attenuated inflammatory gene expression following MI/R. Using mice deficient in either C1q or MBL, or effector proteins downstream of both, we propose to identify the events leading to tissue destruction following xperimental MI/R. In this proposal, we will investigate the role of MBL vs C1q (i.e. lectin vs. classical pathway) following MI/R. We hypothesize that irreversible cardiac damage following MI/R is dependent on MBL and lectin complement pathway activation. The specific aims are as follows: 1) Characterize MBL-dependent complement activation in the initiation of MI/R injury, and additionally evaluate the role of C1q in IMI/R; 2) Determine the mechanism of MBL-dependent injury following MI/R.