title: Plasminogen activator inhibitor-1 and its cofactor vitronectin stabilize arterial thrombi after vascular injury in mice.
abstract: BACKGROUND
  The origin and contribution of plasminogen activator inhibitor-1 (PAI-1) and its cofactor vitronectin (VN) to arterial thrombosis/thrombolysis in vivo is controversial.
  
  
  RESULTS
  Ferric chloride was used to induce carotid artery injury in 97 wild-type (WT), 84 PAI-1-/-, and 84 VN-/- mice. Complete thrombotic occlusion was observed in 70% of PAI-1-/- mice versus 92% of WT (P:<0.001) and 87% of VN-/- (P:=0.015) mice. In vessels that occluded, mean times to occlusion were significantly longer in PAI-1-/- than in WT or VN-/- mice. The initial thrombotic response of VN-/- mice was similar to that of WT mice, but their thrombi were unstable and frequently embolized. As a result, the patency rate of carotid vessels 30 minutes after injury was as high in VN-/- mice (36%) as in PAI-1-/- mice (which demonstrate progressive thrombolysis) and significantly higher than that of WT mice (12%; P:=0.013). Histochemical and reverse transcription-polymerase chain reaction studies revealed an early upregulation of PAI-1 mRNA and protein expression in the thrombus and the vessel wall, which persisted for >/=1 week. VN protein also accumulated after injury, but VN mRNA levels remained low at all times.
  
  
  CONCLUSIONS
  PAI-1 and VN participate in the thrombotic response to arterial injury by preventing premature thrombus dissolution and embolization. The accumulation of PAI-1 in the thrombus/vessel wall after injury may result, at least in part, from local synthesis, whereas the VN protein appears to be derived from plasma.
authors.affiliation: Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: S
authors.initials: S
authors.lastname: Konstantinides
authors.forename: K
authors.initials: K
authors.lastname: Schäfer
authors.forename: T
authors.initials: T
authors.lastname: Thinnes
authors.forename: D J
authors.initials: DJ
authors.lastname: Loskutoff
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D001775:Blood Circulation; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020212:Carotid Artery Injuries / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D002712:Chlorides; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage; D015870:Gene Expression; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000503:physiopathology*; D013997:Time Factors; D014746:Vimentin / Q000032:analysis; D019096:Vitronectin / Q000235:genetics / Q000502:physiology*
chemical_list: D000199:Actins; D002712:Chlorides; D005290:Ferric Compounds; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014746:Vimentin; D019096:Vitronectin; C024555:ferric chloride