Endogenous and natural complement inhibitor attenuates myocardial injury and arterial thrombogenesis
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Circulation. Supplement |
Volume | 126 |
Issue number | 18 |
Pages (from-to) | 2227-35 |
Number of pages | 9 |
ISSN | 0009-7322 |
DOIs | |
Publication status | Published - 30 Oct 2012 |
- Animals, Anticoagulants, Carotid Artery Thrombosis, Complement C3, Complement Pathway, Mannose-Binding Lectin, Depression, Chemical, Disease Models, Animal, Drug Evaluation, Preclinical, Humans, Lectins, Mannose-Binding Protein-Associated Serine Proteases, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Cardiovascular, Models, Immunological, Molecular Weight, Multiprotein Complexes, Myocardial Infarction, Myocardial Reperfusion Injury, Protein Binding, Recombinant Fusion Proteins, Ultrasonography, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Research areas
ID: 172399434