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
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.