Integrins alpha(v)beta(3) and alpha(v)beta(5) mediate VSMC migration and are elevated during neointima formation in the rat aorta

Neointima formation involves tissue expression of matrix proteins and growt h factors. The role of alpha (v)beta (3), but not alpha (v)beta (5) integri n in vascular cells has been sufficiently investigated. The aim of the pres ent study was to determine and compare the function of alpha (v)beta (3) an d alpha (v)beta (5) integrins in rat aortic (RASMC) and human coronary vasc ular smooth muscle cells (HCSMC) and to characterize their expression accom panying neointima formation in vivo. RASMC and HCSMC express alpha (v)beta (3) and alpha (v)beta (5) integrin subunits. The alpha (v)beta (5) integrin predominantly mediated adhesion of RASMCs to vitronectin and spreading on vitronectin via RGD-binding sequences. In contrast, the alpha (v)beta (3) i ntegrin did not contribute to the adhesion and spreading on fibronectin, vi tronectin, gelatin or collagen I coated layers. PDGF-directed migration thr ough gelatin coated membranes involved both alpha (v)beta (3) and alpha (v) beta (5) integrins. Selective blocking antibodies for alpha (v)beta (3) and alpha (v)beta (5) inhibited migration of RASMC and HCSMC by more than 60 % (p < 0.01). Integrin expression was studied in vivo in thoracic aorta of S prague Dawley rats before and after balloon injury. In situ hybridization d emonstrated low signals for <alpha>(v), beta (3) and beta (5) mRNA in uninj ured aorta, which increased significantly at 14 days, localized predominant ly in the neointima. Northern analysis of aorta after 14 days of injury als o demonstrated an upregulation of alpha (v), beta (3) and beta (5) mRNA com pared to uninjured aorta. Consistent with the increase in message levels, i ncreased integrin protein expression was seen in the neointima after 7 and 14 days. This study provides evidence that alpha (v)beta (3) and alpha (v)b eta (5) are elevated during neointima formation in the rat and indicates a novel role for alpha (v)beta (5) participating in mechanisms regulating smo oth muscle cell migration.