title: Plasminogen activation: a mediator of vascular smooth muscle cell apoptosis in atherosclerotic plaques.
abstract: BACKGROUND
  Apoptosis of vascular cells is considered to be a major determinant of atherosclerotic plaque vulnerability and potential rupture. Plasmin can be generated in atherosclerotic plaques and recent in vitro data suggest that plasminogen activation may trigger vascular smooth muscle cell (VSMC) apoptosis.
  
  
  OBJECTIVE
  To determine whether plasminogen activation may induce aortic VSMC apoptosis ex vivo and in vivo.
  
  
  RESULTS
  Mice with single or combined deficiencies of apolipoprotein E (ApoE) and plasminogen activator inhibitor-1 (PAI-1) were used. Ex vivo incubation with plasminogen of isolated aortic tunica media from PAI-1-deficient mice induced plasminogen activation and VSMC apoptosis, which was inhibited by alpha2-antiplasmin. In vivo, levels of plasmin, active caspase 3 and VSMC apoptotic index were significantly higher in atherosclerotic aortas from mice with combined ApoE and PAI-1 deficiencies than in those from littermates with single ApoE deficiency. A parallel decrease in VSMC density was observed.
  
  
  CONCLUSIONS
  These data strongly suggest that plasminogen activation may contribute to VSMC apoptosis in atherosclerotic plaques.
authors.affiliation: Center for Molecular and Vascular Biology, K.U. Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Rossignol
authors.forename: A
authors.initials: A
authors.lastname: Luttun
authors.forename: J L
authors.initials: JL
authors.lastname: Martin-Ventura
authors.forename: F
authors.initials: F
authors.lastname: Lupu
authors.forename: P
authors.initials: P
authors.lastname: Carmeliet
authors.forename: D
authors.initials: D
authors.lastname: Collen
authors.forename: E
authors.initials: E
authors.lastname: Anglès-Cano
authors.forename: H R
authors.initials: HR
authors.lastname: Lijnen
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005341:Fibrinolysin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010958:Plasminogen / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000979:alpha-2-Antiplasmin / Q000494:pharmacology
chemical_list: D001057:Apolipoproteins E; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; D010958:Plasminogen; D005341:Fibrinolysin