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

Article

关键词: SMOOTH-MUSCLE CELLS;    NEOINTIMA FORMATION;    ENDOTHELIAL INJURY;    PAI-1;    THROMBOLYSIS;    FIBRINOLYSIS;    EXPRESSION;    MOUSE;    MODEL;    HEMOSTASIS;   

DOI  :  10.1161/01.CIR.103.4.576

来源: SCIE

【 摘 要 】

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. Methods and 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.

【 授权许可】

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