on April 28, 2005
Published online before print April 28, 2005, doi: 10.1161/01.ATV.0000168415.33812.51
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Submitted on March 15, 2004
Accepted on April 7, 2005
Smad7 Gene Transfer Attenuates Adventitial Cell Migration and Vascular Remodelling After Balloon Injury
Chandike M. Mallawaarachchi ;
From the Division of Cardiovascular Medicine, School of Clinical Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge UK.
* To whom correspondence should be addressed. E-mail: richard.siow{at}kcl.ac.uk.
Objective--Migration of adventitial fibroblasts contributes to arterial remodelling after angioplasty. This study used vascular gene transfer of smad7 to investigate whether antagonism of transforming growth factor-
1 signaling alters luminal loss and adventitial cell migration after balloon injury in rat carotid arteries.
Methods and Results--Adenoviruses coordinating expression of -galactosidase (-gal) and smad7 or -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 -gal positive cells; however, after balloon injury in -gal- and GFP-transfected arteries, -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 -gal resulted in a significant reduction in the number of -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 remodelling and contribution of adventitial fibroblasts to neointima formation after balloon angioplasty. Smad7 may represent a novel therapeutic target to reduce the incidence of restenosis.
Key words: adventitia • restenosis • balloon angioplasty • smad7 • TGF-
1
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