Published Online
on April 21, 2003

A more recent version of this article appeared on May 6, 2003

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Submitted on December 31, 2002
Accepted on February 4, 2003

Single Injection of P-Selectin or P-Selectin Glycoprotein Ligand-1 Monoclonal Antibody Blocks Neointima Formation After Arterial Injury in Apolipoprotein E-Deficient Mice

J. William Phillips MD, Kurt G. Barringhaus MD, John M. Sanders BS, Sean E. Hesselbacher BS, Ann C. Czarnik BS, David Manka PhD, Dietmar Vestweber PhD, Klaus Ley MD, and Ian J. Sarembock MB, ChB, MD^*

From the Department of Medicine, Cardiovascular Division (J.W.P., K.G.B., J.M.S., S.E.H., A.C.C., I.J.S.), the Cardiovascular Research Center (K.L., I.J.S.), and the Department of Biomedical Engineering (D.M., K.L.), University of Virginia Health System, Charlottesville; and the University of Münster, Münster, Germany (D.V.). Dr Manka is currently at the Center for Transgene Technology and Gene Therapy, Leuven, Belgium.

^* To whom correspondence should be addressed. E-mail: ijs4s{at}virginia.edu.

Background--Emerging data suggest that P-selectin, by controlling adhesion of white blood cells, may be important in limiting the response to vascular injury.

Methods and Results--We tested the hypothesis that transient inhibition of P-selectin with either anti-P-selectin monoclonal antibody (mAb) or anti-P-selectin glycoprotein ligand-1 (PSGL-1) mAb would reduce neointima formation in the setting of carotid denudation injury in atherosclerosis-prone apolipoprotein E^-/- mice. Neointima formation at 28 days was reduced significantly, by 50% or 80%, by a single injection on the day of injury of 100 or 200 µg P-selectin mAb RB 40.34 and by 55% by a single injection of 100 µg PSGL-1 mAb 4RA10 (P0.005). In addition, there was a significant reduction in neointimal macrophage content.

Conclusions--These findings demonstrate that transient P-selectin or PSGL-1 blockade at the time of arterial injury significantly limits plaque macrophage content and neointima formation in a dose-dependent manner after carotid denudation injury in apolipoprotein E^-/- mice.

Key words: antibodies • arteries • atherosclerosis • cell adhesion molecules • inflammation

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