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(Circulation. 1999;100:849-854.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Antibody Blockade of Thrombospondin Accelerates Reendothelialization and Reduces Neointima Formation in Balloon-Injured Rat Carotid Artery

Donghui Chen, MD; Takayuki Asahara, MD; Kevin Krasinski, BA; Bernhard Witzenbichler, MD; Jihong Yang, MD; Meredith Magner, BA; Marianne Kearney, BS; William A. Frazier, PhD; Jeffrey M. Isner, MD; Vicente Andrés, PhD

From the Department of Medicine (Cardiology), St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass (D.C., T.A., K.K., B.W., J.Y., M.M., M.K., J.M.I., V.A.); the Unit of Vascular Biology, Instituto de Biomedicina, Consejo Superior de Investigaciones Científicas, Valencia, Spain (V.A.); and the Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Mo (W.A.F.).

Correspondence to Vicente Andrés, PhD, Instituto de Biomedicina (C.S.I.C.), Jaime Roig 11, 46010 Valencia, Spain. E-mail vandres{at}ibv.csic.es

Background—Remodeling of the extracellular matrix plays an important role during the pathogenesis of atherosclerosis and restenosis. The matrix glycoprotein thrombospondin-1 (TSP1) inhibits endothelial cell proliferation and migration in vitro. In contrast, TSP1 facilitates the growth and migration of cultured vascular smooth muscle cells. Accordingly, we investigated the hypothesis that administration of anti-TSP1 antibody could facilitate reendothelialization and inhibit neointimal thickening in balloon-injured rat carotid artery.

Methods and Results—Sprague-Dawley rats were subjected to left common carotid artery denudation, after which arteries were treated with C6.7 anti-TSP1 or control antibody. Evans blue dye staining 2 weeks after injury disclosed significantly increased reendothelialization in arteries treated with C6.7 antibody compared with the control group, and this effect was associated with increased number of proliferating cell nuclear antigen–positive endothelial cells. In contrast, treatment with C6.7 antibody decreased the number of proliferating cell nuclear antigen–positive vascular smooth muscle cells in the injured arterial wall. Neointimal thickening was correspondingly attenuated to a statistically significant degree in arteries receiving C6.7 antibody versus the control group at both the 2-week and 4-week time points.

Conclusions—Intra-arterial delivery of antibody against TSP1 facilitated reendothelialization and reduced neointimal lesion formation after balloon denudation.

Key Words: antibodies • angioplasty • endothelium • carotid arteries • muscle, smooth

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