OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
Authors: Kurt A Zimmerman; Dongqi Xing; Manuel A Pallero; Ailing Lu; Masahito Ikawa; Leland Black; Kenneth L Hoyt; Janusz H Kabarowski; Marek Michalak; Joanne E Murphy-Ullrich Journal: J Vasc Res Date: 2016-02-25 Impact factor: 1.934
Authors: Mark W Majesky; Xiu Rong Dong; Virginia Hoglund; William M Mahoney; Guenter Daum Journal: Arterioscler Thromb Vasc Biol Date: 2011-07 Impact factor: 8.311
Authors: Rishi Kundi; Scott T Hollenbeck; Dai Yamanouchi; Brad C Herman; Rachel Edlin; Evan J Ryer; Chunjie Wang; Shirling Tsai; Bo Liu; K Craig Kent Journal: Cardiovasc Res Date: 2009-07-01 Impact factor: 10.787
Authors: Kurt R Stenmark; Eva Nozik-Grayck; Evgenia Gerasimovskaya; Adil Anwar; Min Li; Suzette Riddle; Maria Frid Journal: Compr Physiol Date: 2011-01 Impact factor: 9.090