Chen D, Asahara T, Krasinski K, Witzenbichler B, Yang J, Magner M, Kearney M, Frazier W A, Isner J M, Andrés V
Department of Medicine (Cardiology), St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass, USA.
Circulation. 1999 Aug 24;100(8):849-54. doi: 10.1161/01.cir.100.8.849.
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.
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.
Intra-arterial delivery of antibody against TSP1 facilitated reendothelialization and reduced neointimal lesion formation after balloon denudation.
细胞外基质重塑在动脉粥样硬化和再狭窄的发病机制中起重要作用。基质糖蛋白血小板反应蛋白-1（TSP1）在体外抑制内皮细胞增殖和迁移。相反，TSP1促进培养的血管平滑肌细胞的生长和迁移。因此，我们研究了以下假说：给予抗TSP1抗体可促进球囊损伤大鼠颈动脉的再内皮化并抑制内膜增厚。
对Sprague-Dawley大鼠进行左颈总动脉剥脱术，术后用C6.7抗TSP1抗体或对照抗体处理动脉。损伤后2周的伊文思蓝染料染色显示，与对照组相比，用C6.7抗体处理的动脉再内皮化显著增加，且这种作用与增殖细胞核抗原阳性内皮细胞数量增加有关。相反，用C6.7抗体处理可减少损伤动脉壁中增殖细胞核抗原阳性血管平滑肌细胞的数量。在2周和4周时间点，与对照组相比，接受C6.7抗体的动脉内膜增厚相应减轻至具有统计学意义的程度。
动脉内递送抗TSP1抗体可促进球囊剥脱术后的再内皮化并减少内膜病变形成。
