The mannose-binding lectin pathway is a significant contributor to reperfusion injury in the type 2 diabetic heart.
The severity of ischaemic heart disease is markedly enhanced in type 2 diabetes. We recently reported that complement activation exacerbates I/R injury in the type 2 diabetic heart. The purpose of this study was to isolate and examine MBL pathway activation following I/R injury in the diabetic heart. ZLC and ZDF rats underwent 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion. Two different groups of ZDF rats were treated with either FUT-175, a broad complement inhibitor, or P2D5, a monoclonal antibody raised against rat MBL-A. ZDF rats treated with FUT175 and P2D5 had significantly decreased myocardial infarct size, C3 deposition and neutrophil accumulation compared with untreated ZDF controls. Taken together, these findings indicate that the MBL pathway plays a key role in the severity of complement-mediated I/R injury in the type 2 diabetic heart.
La Bonte
Laura R
LR
Department of Surgery, University of Arizona, Tucson, AZ 85724-5071, USA.
Dokken
Betsy
B
Davis-Gorman
Grace
G
Stahl
Gregory L
GL
McDonagh
Paul F
PF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001550:Benzamidines; D003176:Complement C3 / Q000378:metabolism; D051056:Complement Inactivating Agents / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D037601:Mannose-Binding Lectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009203:Myocardial Infarction / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020556:Neutrophil Infiltration; D051381:Rats; D011924:Rats, Zucker; D013997:Time Factors
D000911:Antibodies, Monoclonal; D001550:Benzamidines; D003176:Complement C3; D051056:Complement Inactivating Agents; D006146:Guanidines; D037601:Mannose-Binding Lectin; D018799:Intercellular Adhesion Molecule-1; C069858:mannose binding protein A; C032855:nafamostat