Integrins α v β 3 and α v β 5 mediate VSMC migration and are elevated during neointima formation in the rat aorta

Abstract

Neointima formation involves tissue expression of matrix proteins and growth factors. The role of alphavbeta3, but not alphavbeta5 integrin in vascular cells has been sufficiently investigated. The aim of the present study was to determine and compare the function of alphavbeta3 and alphavbeta5 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 alphavbeta3 and alphavbeta5 integrin subunits. The alphavbeta5 integrin predominantly mediated adhesion of RASMCs to vitronectin and spreading on vitronectin via RGD-binding sequences. In contrast, the alphavbeta3 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 alphavbeta3 and alphavbeta5 integrins. Selective blocking antibodies for alphavbeta3 and alphavbeta5 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 alphav, beta3 and beta5 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 alphav, beta3 and beta5 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 alphavbeta3 and alphavbeta5 are elevated during neointima formation in the rat and indicates a novel role for alphavbeta5 participating in mechanisms regulating smooth muscle cell migration.

βig-h3 triggers signaling pathways mediating adhesion and migration of vascular smooth muscle cells through αvβ5 integrin

“…Previous studies have shown that the αvβ3 and αvβ5 integrins mediate VSMC migration on vitronectin (Clyman et al, 1992;Kappert et al, 2001;Stawowy et al, 2004). In this regard, we investigated the effects of function-blocking antibodies against αvβ3 and αvβ5 integrins on the adhesion of aortic VSMCs to βig-h3.…”

“…For example, vitronectin has been shown to mediate VSMC adhesion mainly through the αvβ5 integrin but not through the αvβ3 integrin (Clyman et al, 1992;Kappert et al, 2001;Stawowy et al, 2004). Both the αvβ3 and αvβ5 integrins are elevated during neointima formation in injured aorta (Kappert et al, 2001). We showed here that similar to vitronectin, βig-h3 mediates VSMC adhesion and migration through the αvβ5 integrin but not the αvβ3 integrin.…”

Latent Transforming Growth Factor-β Binding Protein-1, a Component of Latent Transforming Growth Factor-β Complex, Accelerates the Migration of Aortic Smooth Muscle Cells in Diabetic Rats Through Integrin-β3

“…Kappert et al (45) reported that PDGF-directed migration of rat and human SMCs through gelatin-coated membranes involved not only ␣ v ␤ 3 -integrin but also ␣ v ␤ 5 -integrin by experiments using blocking antibodies to these integrins. Moreover, Liu et al (46) showed that integrin-␣ v ␤ 3 is involved in the migration of rat vascular adventitial fibroblasts stimulated by basic fibroblast growth factor but not by PDGF.…”

Tensegrin in context

“…Some of the integrins that are poorly expressed in contractile VSMCs, especially a2b1, a5b1 and avb3, become more prominent in non-contractile state 33 and mediate VSMC migration. [34][35][36][37] a2b1 integrin, a collagen receptor, has been implicated in platelet-derived growth factor (PDGF)-induced VSMC migration. 34 It has been reported that stress fiber disassembly by fibroblast growth factor may promote the differential utilization of a2b1 integrin for VSMC motility.…”

“…avb3 and avb5 integrins both mediate VSMC migration. 37 Moreover, endothelin1, which is known to enhance contractility, inhibits av expression. 40 Therefore, it appears that av integrin is downregulated in conditions of increased contractile forces.…”