Mallawaarachchi Chandike M, Weissberg Peter L, Siow Richard C M
Division of Cardiovascular Medicine, School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1383-7. doi: 10.1161/01.ATV.0000168415.33812.51. Epub 2005 Apr 28.
Migration of adventitial fibroblasts contributes to arterial remodeling after angioplasty. This study used vascular gene transfer of smad7 to investigate whether antagonism of transforming growth factor-beta1 signaling alters luminal loss and adventitial cell migration after balloon injury in rat carotid arteries.
Adenoviruses coordinating expression of beta-galactosidase (beta-gal) and smad7 or beta-gal and green fluorescent protein (GFP) were applied to the perivascular surface of common carotid arteries. Balloon injury was performed 4 days after gene transfer, and animals were killed at 3, 7, and 14 days after injury. Uninjured arteries only expressed adventitial beta-gal positive cells; however, after balloon injury in beta-gal- and GFP-transfected arteries, beta-gal-positive cells were observed within the medial layer of vessels and contributed to the population of cells within the neointima at 7 to 14 days. Overexpression of smad7 and beta-gal resulted in a significant reduction in the number of beta-gal-labeled cells in the neointima, concomitant with reduced luminal loss and decreased adventitial collagen content.
We provide the first evidence that vascular smad7 overexpression attenuates remodeling and contribution of adventitial fibroblasts to neointima formation after balloon angioplasty. Smad7 may represent a novel therapeutic target to reduce the incidence of restenosis.
血管外膜成纤维细胞的迁移有助于血管成形术后的动脉重塑。本研究采用血管基因转移技术将Smad7导入大鼠颈动脉，以探讨转化生长因子-β1信号通路的拮抗作用是否能改变球囊损伤后管腔狭窄及外膜细胞迁移情况。
将协同表达β-半乳糖苷酶（β-gal）和Smad7或β-gal和绿色荧光蛋白（GFP）的腺病毒应用于大鼠颈总动脉的血管外膜表面。基因转移4天后进行球囊损伤，损伤后3天、7天和14天处死动物。未损伤的动脉仅表达外膜β-gal阳性细胞；然而，在β-gal和GFP转染的动脉球囊损伤后，在内膜层观察到β-gal阳性细胞，且在损伤后7至14天，这些细胞成为新生内膜细胞群体的一部分。Smad7和β-gal的过表达导致新生内膜中β-gal标记细胞数量显著减少，同时管腔狭窄减轻，外膜胶原含量降低。
我们首次证明血管Smad7过表达可减轻球囊血管成形术后的重塑以及外膜成纤维细胞对新生内膜形成的作用。Smad7可能是降低再狭窄发生率的一个新的治疗靶点。
