Antibody blockade of thrombospondin accelerates reendothelialization and reduces neointima formation in balloon-injured rat carotid artery

Background-Remodeling of the extracellular matrix plays an important role d uring the pathogenesis of atherosclerosis and restenosis. The matrix glycop rotein thrombospondin-l (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 reend othelialization and inhibit neointimal thickening in balloon-injured rat ca rotid artery. Methods and Results-Sprague-Dawley rats were subjected to left common carot id artery denudation, after which arteries were treated with C6.7 anti-TSP1 or control antibody. Evans blue dye staining 2 weeks after injury disclose d 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 endoth elial cells. In contrast, treatment with C6.7 antibody decreased the number of proliferating cell nuclear antigen-positive vascular smooth muscle cell s in the injured arterial wall. Neointimal thickening was correspondingly a ttenuated 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 re endothelialization and reduced neointimal lesion formation after balloon de nudation.