title: Complement C3 is a novel plasma clot component with anti-fibrinolytic properties.
abstract: METHODS
  Increased plasma clot density and prolonged lysis times are associated with cardiovascular disease. In this study, we employed a functional proteomics approach to identify novel clot components which may influence clot phenotypes.
  
  
  RESULTS
  Analysis of perfused, solubilised plasma clots identified inflammatory proteins, including complement C3, as novel clot components. Analysis of paired plasma and serum samples confirmed concentration-dependent incorporation of C3 into clots. Surface plasmon resonance indicated high-affinity binding interactions between C3 and fibrinogen and fibrin. Turbidimetric clotting and lysis assays indicated C3 impaired fibrinolysis in a concentration-dependent manner, both in vitro and ex vivo.
  
  
  CONCLUSIONS
  These data indicate functional interactions between complement C3 and fibrin leading to prolonged fibrinolysis. These interactions are physiologically relevant in the context of protection following injury and suggest a mechanistic link between increased plasma C3 concentration and acute cardiovascular thrombotic events.
authors.affiliation: Division of Cardiovascular & Diabetes Research, Leeds Institute of Genetics Health & Therapeutics, University of Leeds, UK.
authors.forename: Joanna-Marie
authors.initials: JM
authors.lastname: Howes
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Richardson
authors.forename: Kerrie A
authors.initials: KA
authors.lastname: Smith
authors.forename: Verena
authors.initials: V
authors.lastname: Schroeder
authors.forename: Riyaz
authors.initials: R
authors.lastname: Somani
authors.forename: Anna
authors.initials: A
authors.lastname: Shore
authors.forename: Katharina
authors.initials: K
authors.lastname: Hess
authors.forename: Ramzi
authors.initials: R
authors.lastname: Ajjan
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Pease
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Keen
authors.forename: Kristina F
authors.initials: KF
authors.lastname: Standeven
authors.forename: Angela M
authors.initials: AM
authors.lastname: Carter
mesh_terms: D003176:Complement C3 / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D010949:Plasma / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism*
chemical_list: D003176:Complement C3; D017242:Complement Factor H; D005337:Fibrin; D005340:Fibrinogen