Plasminogen activator inhibitor-1 and its cofactor vitronectin stabilize arterial thrombi after vascular injury in mice

Citation
S. Konstantinides et al., Plasminogen activator inhibitor-1 and its cofactor vitronectin stabilize arterial thrombi after vascular injury in mice, CIRCULATION, 103(4), 2001, pp. 576-583
Citations number
32
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
00097322 → ACNP
Volume
103
Issue
4
Year of publication
2001
Pages
576 - 583
Database
ISI
SICI code
0009-7322(20010130)103:4<576:PAIAIC>2.0.ZU;2-5
Abstract
Background-The origin and contribution of plasminogen activator inhibitor-1 (PAI-1) and its cofactor vitronectin (VN) to arterial thrombosis/thromboly sis in vivo is controversial. Methods and Results-Ferric chloride was used to induce carotid artery injur y 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 oc clusion 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 thrombolysi s) and significantly higher than that of WT mice (12%; P=0.013). Histochemi cal and reverse transcription-polymerase chain reaction studies revealed an early upregulation of PAI-1 mRNA and protein expression in the thrombus an d the vessel wall, which persisted for <greater than or equal to>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 b e derived from plasma.