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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1383.)
© 2005 American Heart Association, Inc.

Vascular Biology

Smad7 Gene Transfer Attenuates Adventitial Cell Migration and Vascular Remodeling After Balloon Injury

Chandike M. Mallawaarachchi; Peter L. Weissberg; Richard C.M. Siow

From the Division of Cardiovascular Medicine, School of Clinical Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.

Correspondence to Richard C.M. Siow, PhD, Cardiovascular Division, King’s College, University of London, Guy’s Hospital Campus, London SE1 1UL. E-mail richard.siow{at}kcl.ac.uk

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-ß1 signaling alters luminal loss and adventitial cell migration after balloon injury in rat carotid arteries.

Methods and Results— Adenoviruses coordinating expression of ß-galactosidase (ß-gal) and smad7 or ß-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 ß-gal positive cells; however, after balloon injury in ß-gal- and GFP-transfected arteries, ß-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 ß-gal resulted in a significant reduction in the number of ß-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.

This study investigates whether perivascular adenoviral smad7 gene transfer antagonises TGF-ß1 signaling to decrease adventitial cell migration after balloon injury in rat carotid arteries. Smad7 overexpression attenuated the contribution of adventitial cells to neointima formation after vascular injury, concomitant with reduced luminal loss and adventitial collagen content.

Key Words: adventitia • restenosis • balloon angioplasty • smad7 • TGF-ß1

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