Antibody blockade of thrombospondin accelerates reendothelialization and reduces neointima formation in balloon-injured rat carotid artery
Antibody blockade of thrombospondin accelerates reendothelialization and reduces neointima formation in balloon-injured rat carotid artery
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DOI：
10.1161/01.cir.100.8.849
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发表时间：
1999-08-24
期刊：
影响因子：
37.8
通讯作者：
Andrés, V
中科院分区：
文献类型：
--
作者：
Chen, DH;Asahara, T;Andrés, V
细胞外基质的重塑在动脉粥样硬化和再狭窄的发病机制中起着重要作用。基质糖蛋白血小板反应蛋白-1（TSP 1）在体外抑制内皮细胞增殖和迁移。相反，TSP 1促进培养的血管平滑肌细胞的生长和迁移。因此，我们调查的假设，即管理抗TSP 1抗体可以促进再内皮化和抑制新生内膜增厚在球囊损伤大鼠颈动脉artery.Methods和Results-Sprague-道利大鼠进行左颈总动脉剥脱，动脉后，用C6.7抗TSP 1或对照抗体。与对照组相比，损伤后2周的Evans蓝染色显示C6.7抗体治疗的动脉中再内皮化显著增加，并且这种效果与增殖细胞核抗原阳性内皮细胞数量的增加相关。相比之下，C6.7抗体治疗减少了受损动脉壁中增殖细胞核抗原阳性血管平滑肌细胞的数量。新生内膜增厚相应衰减到一个统计学显着程度的动脉接受C6.7抗体与对照组在2周和4周的时间points. Conclusions动脉内递送的抗体对TSP 1促进再内皮化和减少球囊剥脱后新生内膜病变的形成。
Background-Remodeling of the extracellular matrix plays an important role during the pathogenesis of atherosclerosis and restenosis. The matrix glycoprotein 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 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.