© 1999 American Heart Association, Inc.
Integrative Physiology |
Decreased Neointimal Thickening After Arterial Wall Injury in Inducible Nitric Oxide Synthase Knockout Mice
Presented in part at the 70th Scientific Sessions of the American Heart Association, Orlando, Fla, November 9–12, 1997.
From the Atherosclerosis Research Center (K.-Y.C., P.D., J.Z., S.K., P.K.S., B.C.), Burns and Allen Research Institute, Division of Cardiology, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, California, and the Department of Medicine (J.N.), Lund University, University Hospital MAS, Malmö, Sweden.
Correspondence to Kuang-Yuh Chyu, MD, PhD, Division of Cardiology, Cedars-Sinai Medical Center, Davis Building, Room 1026, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail Chyuk{at}cshs.org
Abstract—Mechanical injury in
vivo results in the expression of the inducible form of nitric oxide
synthase (iNOS) in vascular smooth muscle cells. However, the role of
iNOS in modulating neointima formation after
arterial wall injury is not clear. To determine whether the
induction of iNOS gene expression promotes or attenuates the
neointimal response to injury, we used a murine model of
perivascular injury induced by placing a periadventitial collar around
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 significantly less in the iNOS-KO mice compared
with the wild-type mice at 21 days. Injury-induced proliferation of
medial cells and vascular cell adhesion molecule-1 expression were also
attenuated in iNOS-KO mice compared with wild-type mice. The induction
of iNOS and the activation of the nuclear factor-
B–mediated pathway
were also demonstrated in an in vitro injury model. We conclude that
mechanical injury in vivo and in vitro induces iNOS expression and that
lack of iNOS expression attenuates neointima formation
after perivascular arterial injury. Taken together, these
findings suggest that iNOS expression after vascular injury may promote
neointima formation.
Key Words: nuclear factor-B • vascular cell adhesion molecule-1 • nitric oxide synthase • mice, knockout • neointima
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