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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:201.)
© 2001 American Heart Association, Inc.

Vascular Biology

Endothelial NO Synthase Overexpression Inhibits Lesion Formation in Mouse Model of Vascular Remodeling

Seinosuke Kawashima; Tomoya Yamashita; Masanori Ozaki; Yoshitaka Ohashi; Hiroshi Azumi; Nobutaka Inoue; Ken-ichi Hirata; Yoshitake Hayashi; Hiroshi Itoh; Mitsuhiro Yokoyama

From the First Department of Internal Medicine (S.K., T.Y., M.O., Y.O., N.I., K.H., M.Y.) and the First Department of Pathology (H.A., Y.H., H.I.), Kobe University School of Medicine, Kobe, Japan.

Abstract—NO produced by endothelial NO synthase (eNOS) plays important roles in the regulation of vascular tone and structure. The purpose of this study was to clarify the role of eNOS-derived NO on vascular remodeling by use of eNOS-transgenic (eNOS-Tg) mice. The common carotid artery was ligated just proximal to the carotid bifurcation. Four weeks later, the proximal carotid artery of the ligation site was histologically examined. In this vascular remodeling model, the endothelium remains uninjured, but neointimal and medial thickening occurs in combination with a reduction in vascular diameter at the proximal portion of the ligation. At 4 weeks after ligation, the respective neointimal and medial areas in wild-type mice were 17 200±1100 and 24 300±1500 µm², whereas both were reduced to 8000±1900 (P<0.01) and 18 400±700 µm² (P<0.01) in eNOS-Tg mice (n=8). Total vascular area was not different between the 2 genotypes. N^G-Nitro-L-arginine methyl ester treatment increased neointimal and medial areas to the same extent in both genotypes. Leukocyte infiltration was observed in the luminal side of the vessel, but the number of infiltrating cells was significantly attenuated in eNOS-Tg mice compared with wild-type mice. This reduction of leukocyte infiltration in eNOS-Tg mice was associated with reduced expressions of intracellular adhesion molecule-1 and vascular cellular adhesion molecule-1 on the endothelium. In conclusion, chronic eNOS overexpression in the endothelium reduced leukocyte infiltration and inhibited neointimal formation and medial thickening. Our data provide the evidence for the regulatory role of NO from the endothelium on vascular structure integrity.

Key Words: nitric oxide • endothelial nitric oxide synthase • transgenic mouse • vascular remodeling • intimal thickening

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