IMPAIRED ARTERIAL NEOINTIMA FORMATION IN MICE WITH DISRUPTION OF THE PLASMINOGEN GENE

To define the role of plasminogen (Plg) in the smooth muscle cell resp onse after arterial wall injury, neointima formation was evaluated aft er electric injury of the femoral artery in plasminogen-deficient (Plg (-/-)) mice. The injury destroyed all medial smooth muscle cells, denu ded the injured segment of intact endothelium, and induced transient p latelet-rich mural thrombosis. In wild-type (Plg(+/+)) mice, vascular wound healing was characterized by lysis of the thrombus, transient in filtration of inflammatory cells, and progressive removal of necrotic debris and thrombosis. Topographic analysis revealed repopulation of t he media and accumulation in the neointima of smooth muscle cells orig inating from the noninjured borders, which progressed into the necroti c center. In Plg(-/-) mice, wound healing was significantly impaired w ith delayed removal of necrotic debris, reduced leucocyte infiltration and smooth muscle cell accumulation, and decreased neointima formatio n. Smooth muscle cells accumulated at the uninjured borders, but faile d to migrate into the necrotic center. Proliferation of smooth muscle cells was not affected by Plg deficiency. Evans blue staining revealed no genotypic differences in reendothelialization. Thus, Plg plays a s ignificant role in vascular wound healing and arterial neointima forma tion after injury, most likely by affecting cellular migration.