Decreased neointimal thickening after arterial wall injury in inducible nitric oxide synthase knockout mice

Mechanical injury in vivo results in the expression of the inducible form o f nitric oxide synthase (iNOS) in vascular smooth muscle cells. However, th e role of iNOS in modulating neointima formation after arterial wall injury is not clear. To determine whether the induction of iNOS gene expression p romotes or attenuates the neointimal response to injury, we used a murine m odel of perivascular injury induced by placing a periadventitial collar aro und the carotid arteries in both wild-type and iNOS knockout mice (iNOS-KO mice), Periadventitial injury induced iNOS expression in the wild-type but not the iNOS-KO mice. Neointimal area and the intima/media ratio were signi ficantly less in the iNOS-KO mice compared with the wild-type mice at 21 da ys. Injury-induced proliferation of medial cells and vascular cell adhesion molecule-1 expression were also attenuated in iNOS-KO mice compared with w ild-type mice. The induction of iNOS and the activation of the nuclear fact or-kappa B-mediated pathway were also demonstrated in an in vitro injury mo del, We conclude that mechanical injury in vivo and in vitro induces iNOS e xpression and that lack of iNOS expression attenuates neointima formation a fter perivascular arterial injury. Taken together, these findings suggest t hat iNOS expression after vascular injury may promote neointima formation.