title: Local complement activation triggers neutrophil recruitment to the site of thrombus formation in acute myocardial infarction.
abstract: Atherosclerotic plaque rupture with subsequent mural thrombus formation is considered the main event compromising epicardial flow in acute myocardial infarction (AMI). However, the precise mechanisms underlying acute coronary occlusion are unknown. We compared the proteomic profiles of systemic plasma and plasma derived from the site of thrombus formation of patients with AMI by two-dimensional gel electrophoresis and ELISA. We identified a local activation of the complement system, with selective accumulation of the complement activator C-reactive protein (CRP) and the downstream complement effectors C3a and C5a. CRP in coronary thrombus co-localised with C1q and C3 immunoreactivities, suggesting classical complement activation. In vitro, coronary thrombus derived plasma enhanced neutrophil chemotaxis in a C5a dependent fashion. In vivo, neutrophil accumulation at the site of thrombus formation paralleled the time delay from symptom onset to first balloon inflation or aspiration, and was correlated with C5a and enzymatic infarct size. We present the first direct evidence for localised complement activation in acute coronary thrombi. Our data indicate that local complement effectors amplify the vascular occlusion process in AMI by enhanced neutrophil recruitment.
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Distelmaier
authors.forename: Christopher
authors.initials: C
authors.lastname: Adlbrecht
authors.forename: Johannes
authors.initials: J
authors.lastname: Jakowitsch
authors.forename: Susanne
authors.initials: S
authors.lastname: Winkler
authors.forename: Daniela
authors.initials: D
authors.lastname: Dunkler
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerner
authors.forename: Oswald
authors.initials: O
authors.lastname: Wagner
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
authors.forename: Markus
authors.initials: M
authors.lastname: Kubicek
mesh_terms: D000368:Aged; D002633:Chemotaxis; D003167:Complement Activation; D015926:Complement C3a / Q000737:chemistry; D015936:Complement C5a / Q000737:chemistry; D003165:Complement System Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009203:Myocardial Infarction / Q000097:blood* / Q000473:pathology; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D013927:Thrombosis / Q000473:pathology*
chemical_list: D015926:Complement C3a; D015936:Complement C5a; D003165:Complement System Proteins