Integrins αvβ3 and αvβ5 mediate VSMC migration and are elevated during neointima formation in the rat aorta

Neointima formation involves tissue expression of matrix proteins and growth factors. The role of alpha (v)beta (3), but not alpha (v)beta (5) integrin in vascular cells has been sufficiently investigated. The aim of the present study was to determine and compare the function of alpha (v)beta (3) and alpha (v)beta (5) integrins in rat aortic (RASMC) and human coronary vascular smooth muscle cells (HCSMC) and to characterize their expression accompanying 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) integrin did not contribute to the adhesion and spreading on fibronectin, vitronectin, gelatin or collagen I coated layers. PDGF-directed migration through 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 Sprague Dawley rats before and after balloon injury. In situ hybridization demonstrated low signals for <alpha>(v), beta (3) and beta (5) mRNA in uninjured aorta, which increased significantly at 14 days, localized predominantly in the neointima. Northern analysis of aorta after 14 days of injury also demonstrated an upregulation of alpha (v), beta (3) and beta (5) mRNA compared to uninjured aorta. Consistent with the increase in message levels, increased 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)beta (5) are elevated during neointima formation in the rat and indicates a novel role for alpha (v)beta (5) participating in mechanisms regulating smooth muscle cell migration.