Antagonism of platelet-derived growth factor by perivascular gene transfer attenuates adventitial cell migration after vascular injury: new tricks for old dogs

• Published in: The FASEB journal 2006-08, Vol.20 (10), p.1686-1688
• Main Authors: Mallawaarachchi, Chandike M, Weissberg, Peter L, Siow, Richard C.M
• Format: Article
• Language: English
• Subjects: Angioplasty, Balloon - adverse effects; Animals; Arterial Occlusive Diseases - prevention & control; balloon angioplasty; Carotid Artery Injuries - pathology; Carotid Artery Injuries - therapy; Cell Movement; Fibroblasts - physiology; Green Fluorescent Proteins - administration & dosage; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - pharmacokinetics; Lac Operon - genetics; PDGF; Platelet-Derived Growth Factor - antagonists & inhibitors; Rats; Receptors, Platelet-Derived Growth Factor - administration & dosage; Receptors, Platelet-Derived Growth Factor - genetics; restenosis; Sequence Deletion; Tissue Distribution; Transfection; vascular remodeling
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.05-5435fje

Migration of adventitial fibroblasts contributes to vascular remodeling after angioplasty. This study has used perivascular gene transfer of a truncated platelet-derived growth factor PDGF receptor (PDGFXR) to investigate whether antagonism of PDGF signaling alters adventitial cell migration after balloon injury in rat carotid arteries. Adenoviruses coordinating expression of β-galactosidase (LacZ) and PDGFXR or LacZ and green fluorescent protein (GFP) were applied to the perivascular surface of arteries and balloon injury performed 4 days later. Vessels were excised at 3, 7, and 14 days to determine morphology and gene expression. Uninjured arteries only expressed LacZ positive cells in the adventitial compartment; however, after injury in LacZ and GFP transfected arteries, LacZ positive cells contributed to the population of cells within the media and neointima at 7-14 days. Overexpression of PDGFXR and LacZ resulted in a significant reduction in the number of LacZ labeled cells in the neointima after vascular injury, concomitant with reduced remodeling, collagen content, expression of matrix metalloproteinase-2, and increased levels of tissue inhibitors of metalloproteinase-1 and -2. We provide evidence that perivascular antagonism of PDGF attenuates remodeling and contribution of adventitial fibroblasts to neointima formation after balloon angioplasty. Perivascular gene transfer may represent a therapeutic strategy to reduce the incidence of restenosis.--Mallawaarachchi, C. M., Weissberg, P. L., and Siow, R. C. M. Antagonism of platelet-derived growth factor by perivascular gene transfer attenuates adventitial cell migration after vascular injury: New tricks for old dogs?