Innate immunity in Myocardial Ischemia

描述（由申请人提供）：心肌缺血-再灌注（MI/R）是血管外科和心肌梗死中常见的临床问题。补体激活在与MI/R相关的局部和可能的远程组织损伤中起重要作用。我们实验室的最新证据表明，在体内阻断甘露糖结合凝集素（MBL）可防止补体的沉积和活化，从而显著减少MI/R后的损伤和减弱炎症基因表达。使用C1 q或MBL或两者下游效应蛋白缺陷的小鼠，我们建议鉴定导致实验性MI/R后组织破坏的事件。在这个提议中，我们将研究MBL与C1 q（即凝集素与经典途径）在MI/R后的作用。我们假设MI/R后不可逆的心脏损伤依赖于MBL和凝集素补体途径的激活。具体目的如下：1）表征MI/R损伤起始中MBL依赖性补体激活，并额外评估C1 q在IMI/R中的作用; 2）确定MI/R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.