Endogenous and Natural Complement Inhibitor Attenuates Myocardial Injury and Arterial Thrombogenesis
Background—Coagulation disorders and reperfusion of ischemic myocardium are major causes of morbidity and mortality. Lectin pathway initiation complexes are composed of multimolecular carbohydrate recognition subcomponents and three lectin pathway specific serine proteases. We have recently shown that the lectin pathway specific carbohydrate recognition subcomponent mannose-binding lectin (MBL) plays an essential role in the pathophysiology of thrombosis and ischemia/reperfusion injury. Thus, we hypothesized that the endogenous MBL associated protein, MAP-1, that inhibits complement activation in vitro also could be an in vivo regulator by attenuating myocardial schema/reperfusion injury and thrombogenesis when used at pharmacologic doses in wild type mice.
Methods and Results—MAP-1, in two mouse models, preserves cardiac function, decreases infarct size, decreases C3 deposition, inhibits MBL deposition and prevents thrombogenesis. Further, we also demonstrate that MAP-1 displaces MASP-1, MASP-2 and MASP-3 from the MBL complex.
Conclusions—Our results suggest that the natural, endogenous inhibitor, MAP-1effectively inhibits lectin pathway activation in vivo. MAP-1 at pharmacologic doses represents a novel therapeutic approach for human diseases involving the lectin pathway and its associated MASPs.
- Received June 11, 2012.
- Accepted September 20, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited