Innate immunity in Myocardial Ischemia

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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.