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Updated: Jun 21, 2026

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery
Published on: December 23, 2014
Recombinant plasminogen activator inhibitor-1 inhibits intimal hyperplasia
Jianbo Wu1, Lin Peng, Grainne A McMahon
1Department of Internal Medicine, University of Missouri School of Medicine, and Research Service, Harry S. Truman Memorial Veterans Affairs Hospital, Columbia, MO 65212, USA. wuji@health.missouri.edu
Objective:
Plasminogen activator inhibitor-1 (PAI-1) overexpression is implicated in vascular disease. However, the effects of a primary increase in PAI-1 expression on arterial remodeling are poorly defined. We tested the hypothesis that recombinant PAI-1 inhibits intimal hyperplasia after vascular injury.
Methods And Results:
Rats underwent carotid artery injury and received intraperitoneal injections of saline or mutant forms of PAI-1 for 14 days, including an active stable mutant (PAI-1-14-1b), a mutant lacking anti-PA activity (PAI-1-R), or a mutant defective in vitronectin (VN) binding (PAI-1-K). All forms of PAI-1 significantly inhibited neointima formation, whereas elastase-cleaved PAI-1, which lacks both anti-PA and VN-binding functions, did not. Similar effects were observed in a murine model. However, the antiproliferative effect of PAI-1-R was lost in Vn(-/-) mice, suggesting that PAI-1 can inhibit intimal hyperplasia in vivo by a VN-dependent pathway not involving direct inhibition of proteases. In vitro, recombinant PAI-1 inhibited wild-type vascular smooth muscle cell (VSMC) proliferation, promoted apoptosis, and inhibited migration. These effects were lost in VN-deficient VSMCs.
Conclusions:
Recombinant PAI-1 inhibits intimal hyperplasia by inhibiting proteases and binding VN. VN is a key determinant of the antiproliferative effect of PAI-1 overexpression. PAI-1-R has therapeutic potential to inhibit vascular restenosis without promoting thrombosis.
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