INTRODUCTION: Constrictive remodeling of the neointima results in the late lumen loss and restenosis after balloon angioplasty. Intense expression of alpha8beta1 integrin in the contractile state of vascular smooth muscle cells (VSMCs) and in myofibroblasts led us to hypothesize that it might be involved in the process of late constrictive remodeling. METHODS AND RESULTS: Balloon injury was used to induce neointima formation in the rat carotid artery. Immunohistochemical analysis and immunoconfocal studies showed that late lumen narrowing was concomitant with the up-regulation of smooth muscle alpha-actin and alpha8 integrin in the neointima. The transforming growth factor-beta (TGF-beta)-induced contractile properties of fibroblasts and VSMCs populated in a three-dimensional collagen matrix was associated with up-regulation of alpha8 integrin. TGF-beta-induced myofibroblastic features in Rat1 fibroblasts were impaired in cells pretreated with a small interference RNA silencing the alpha8 integrin gene. CONCLUSION: The close correlation between alpha8 integrin up-regulation in the neointima and late luminal loss and alpha8 integrin being required for contractile properties induced by TGF-beta highlight a possible role for alpha8 integrin in postangioplasty restenosis.
INTRODUCTION: Constrictive remodeling of the neointima results in the late lumen loss and restenosis after balloon angioplasty. Intense expression of alpha8beta1 integrin in the contractile state of vascular smooth muscle cells (VSMCs) and in myofibroblasts led us to hypothesize that it might be involved in the process of late constrictive remodeling. METHODS AND RESULTS:Balloon injury was used to induce neointima formation in the rat carotid artery. Immunohistochemical analysis and immunoconfocal studies showed that late lumen narrowing was concomitant with the up-regulation of smooth muscle alpha-actin and alpha8 integrin in the neointima. The transforming growth factor-beta (TGF-beta)-induced contractile properties of fibroblasts and VSMCs populated in a three-dimensional collagen matrix was associated with up-regulation of alpha8 integrin. TGF-beta-induced myofibroblastic features in Rat1 fibroblasts were impaired in cells pretreated with a small interference RNA silencing the alpha8 integrin gene. CONCLUSION: The close correlation between alpha8 integrin up-regulation in the neointima and late luminal loss and alpha8 integrin being required for contractile properties induced by TGF-beta highlight a possible role for alpha8 integrin in postangioplasty restenosis.
Authors: Amy L Pyle; James B Atkinson; Ambra Pozzi; Jeff Reese; Beate Eckes; Jeffrey M Davidson; Dan L Crimmins; Pampee P Young Journal: Am J Pathol Date: 2008-10-02 Impact factor: 4.307