title: Endogenous and natural complement inhibitor attenuates myocardial injury and arterial thrombogenesis.
abstract: 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.
  
  
  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.
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA 02115, USA.
authors.forename: Vasile I
authors.initials: VI
authors.lastname: Pavlov
authors.forename: Mikkel-Ole
authors.initials: MO
authors.lastname: Skjoedt
authors.forename: Ying
authors.initials: Y
authors.lastname: Siow Tan
authors.forename: Anne
authors.initials: A
authors.lastname: Rosbjerg
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D002341:Carotid Artery Thrombosis / Q000139:chemically induced / Q000188:drug therapy*; D003176:Complement C3 / Q000032:analysis; D037582:Complement Pathway, Mannose-Binding Lectin / Q000187:drug effects* / Q000502:physiology; D003864:Depression, Chemical; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D037102:Lectins / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008955:Models, Cardiovascular; D018448:Models, Immunological; D008970:Molecular Weight; D046912:Multiprotein Complexes / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014463:Ultrasonography; D000097604:Ficolins
chemical_list: D000925:Anticoagulants; D003176:Complement C3; D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D000097604:Ficolins; C577328:MASP-1 protein, mouse; C084067:MASP1 protein, human