Smad7 gene transfer attenuates adventitial cell migration and vascular remodeling after balloon injury.
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.


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.
Mallawaarachchi
Chandike M
CM
Division of Cardiovascular Medicine, School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Weissberg
Peter L
PL
Siow
Richard C M
RC
D000199:Actins / Q000235:genetics; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology; D020212:Carotid Artery Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016893:Carotid Stenosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002465:Cell Movement / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D055502:Secondary Prevention; D015398:Signal Transduction / Q000502:physiology; D051906:Smad7 Protein / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000199:Actins; D051906:Smad7 Protein; C497808:Smad7 protein, rat; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen