P. Carmeliet et al., IMPAIRED ARTERIAL NEOINTIMA FORMATION IN MICE WITH DISRUPTION OF THE PLASMINOGEN GENE, The Journal of clinical investigation, 99(2), 1997, pp. 200-208
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.