(Circulation. 2000;102:1710.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Roles of P-Selectin in Inflammation, Neointimal Formation, and Vascular Remodeling in Balloon-Injured Rat Carotid Arteries
From the First Department of Internal Medicine (S.H., N.W., J.S., K.T., M.I.) and First Department of Pathology (K.N.), Shinshu University School of Medicine, Matsumoto, and Pharmaceutical Frontier Research Laboratories, Japan Tobacco, Yokohama (T.T., S.S.), Japan. Dr Isobe is now at the Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Correspondence to Mitsuaki Isobe, MD, PhD, Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail isobemi.med3{at}med.tmd.ac.jp
Background—P-selectin plays key roles in mediating inflammation through promoting adherence of leukocytes to activated platelets and endothelium. This process is one of the initial events in atherosclerosis and restenosis after coronary angioplasty.
Methods and Results—Using a rat balloon-injury model, we examined
the role of P-selectin in vascular inflammatory processes. In the acute
phase, immunohistochemistry revealed that P-selectin was intensely
expressed on both activated platelets covering the denuded
segment and endothelial cells of the inflamed
adventitial small vessels. Treatment with an anti–P-selectin
monoclonal antibody (MAb) for 8 consecutive days significantly
inhibited neointimal formation at day 14 (42% inhibition;
P<0.05), and this effect persisted at day 56 (40%
inhibition; P<0.01) compared with the control group.
Vascular shrinking accompanying adventitial fibrosis was also
attenuated at day 56. Inhibition of both neointimal
formation and vascular shrinking resulted in the lumen area of the
anti–P-selectin treatment group being 
3 times larger at day 56 than
that of the control group. Accumulation of CD45-positive leukocytes in
the developing neointima, media, and adventitia at day 8
was significantly inhibited by treatment with the anti–P-selectin MAb.
Scanning electron microscopy demonstrated that anti–P-selectin
treatment resulted in a less thrombogenic surface of the
arterial intima, which featured a
pseudoendothelial appearance at day 14 after
injury.
Conclusions—These results suggest that inhibition of P-selectin–mediated leukocyte recruitment prevents the development of neointimal formation, adventitial inflammation, and vascular shrinking and promotes pseudoendothelialization by luminal smooth muscle cells. This treatment thus beneficially affects vascular remodeling after balloon injury in rats.
Key Words: adhesion molecules • leukocytes • platelets • restenosis • remodeling
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