To define the role of
plasminogen (Plg) in the smooth muscle cell response after arterial wall injury,
neointima formation was evaluated after
electric injury of the femoral artery in
plasminogen-deficient (Plg-/-) mice. The injury destroyed all medial smooth muscle cells, denuded the injured segment of intact endothelium, and induced transient platelet-rich mural
thrombosis. In wild-type (Plg+/+) mice, vascular wound healing was characterized by lysis of the
thrombus, transient infiltration of inflammatory cells, and progressive removal of necrotic debris and
thrombosis. Topographic analysis revealed repopulation of the media and accumulation in the
neointima of smooth muscle cells originating from the noninjured borders, which progressed into the necrotic center. In Plg-/- mice, wound healing was significantly impaired with delayed removal of necrotic debris, reduced leucocyte infiltration and smooth muscle cell accumulation, and decreased
neointima formation. Smooth muscle cells accumulated at the uninjured borders, but failed 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 significant role in vascular wound healing and arterial
neointima formation after injury, most likely by affecting cellular migration.