Impaired arterial neointima formation in mice with disruption of the plasminogen gene.
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.
Carmeliet
P
P
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium.
Moons
L
L
Ploplis
V
V
Plow
E
E
Collen
D
D
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000473:pathology; D002455:Cell Division; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000254:growth & development; D005263:Femoral Artery / Q000473:pathology*; D005341:Fibrinolysin / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000254:growth & development*; D010958:Plasminogen / Q000235:genetics*; D013927:Thrombosis; D017539:Tunica Intima / Q000473:pathology*; D014945:Wound Healing
D010958:Plasminogen; D005341:Fibrinolysin