Inhibitory Role of Plasminogen Activator Inhibitor-1 in Arterial Wound Healing and Neointima Formation

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Abstract
Background Plasminogen-deficient mice display impaired vascular wound healing and reduced arterial neointima formation after arterial injury, suggesting that inhibition of plasmin generation might reduce arterial neointima formation. Therefore, we studied the consequences of plasminogen activator inhibitor-1 (PAI-1) gene inactivation and adenoviral PAI-1 gene transfer on arterial neointima formation. Methods and Results Neointima formation was evaluated in PAI-1–deficient (PAI-1−/−) mice with perivascular electric or transluminal mechanical injury. PAI-1 deficiency improved vascular wound healing in both models: the cross-sectional neointimal area was 0.001±0.001 mm2 in PAI-1+/+ and 0.016±0.008 mm2 in PAI-1−/− mice within 1 week after electric injury (P<.02) and 0.055±0.008 mm2 in PAI-1+/+ and 0.126±0.006 mm2 in PAI-1−/− mice within 3 weeks after mechanical injury (P<.001). Proliferation of smooth muscle cells was not affected by PAI-1 deficiency. Topographic analysis of arterial wound healing after elect...