| First Author | Pavlov VI | Year | 2012 |
| Journal | Circulation | Volume | 126 |
| Issue | 18 | Pages | 2227-35 |
| PubMed ID | 23032324 | Mgi Jnum | J:210067 |
| Mgi Id | MGI:5569461 | Doi | 10.1161/CIRCULATIONAHA.112.123968 |
| Citation | Pavlov VI, et al. (2012) Endogenous and natural complement inhibitor attenuates myocardial injury and arterial thrombogenesis. Circulation 126(18):2227-35 |
| abstractText | 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 3 lectin pathway-specific serine proteases. We have recently shown that the lectin pathway-specific carbohydrate recognition subcomponent mannose-binding lectin plays an essential role in the pathophysiology of thrombosis and ischemia/reperfusion injury. Thus, we hypothesized that the endogenous mannose-binding lectin (MBL)/ficolin-associated protein-1 (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 pharmacological doses in wild-type mice. METHODS AND RESULTS: In 2 mouse models, MAP-1 preserves cardiac function, decreases infarct size, decreases C3 deposition, inhibits MBL deposition, and prevents thrombogenesis. Furthermore, we demonstrate that MAP-1 displaces MBL/ficolin-associated serine protease (MASP)-1, MASP-2, and MASP-3 from the MBL complex. CONCLUSIONS: Our results suggest that the natural, endogenous inhibitor MAP-1 effectively inhibits lectin pathway activation in vivo. MAP-1 at pharmacological doses represents a novel therapeutic approach for human diseases involving the lectin pathway and its associated MASPs. |
