Kappert K, Blaschke F, Meehan W P, Kawano H, Grill M, Fleck E, Hsueh W A, Law R E, Graf K
Department of Medicine/Cardiology, Campus Virchow Klinikum der Charité Humboldt Universität Berlin, Germany.
Basic Res Cardiol. 2001 Feb;96(1):42-9. doi: 10.1007/s003950170076.
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.
新生内膜形成涉及基质蛋白和生长因子的组织表达。αvβ3而非αvβ5整合素在血管细胞中的作用已得到充分研究。本研究的目的是确定并比较αvβ3和αvβ5整合素在大鼠主动脉平滑肌细胞（RASMC）和人冠状动脉血管平滑肌细胞（HCSMC）中的功能，并表征它们在体内新生内膜形成过程中的表达情况。RASMC和HCSMC表达αvβ3和αvβ5整合素亚基。αvβ5整合素主要介导RASMC与玻连蛋白的黏附以及通过RGD结合序列在玻连蛋白上的铺展。相比之下，αvβ3整合素对RASMC在纤连蛋白、玻连蛋白、明胶或I型胶原包被层上的黏附及铺展没有作用。血小板衍生生长因子（PDGF）介导的通过明胶包被膜的迁移涉及αvβ3和αvβ5整合素。针对αvβ3和αvβ5的选择性阻断抗体抑制RASMC和HCSMC迁移超过60%（p<0.01）。在球囊损伤前后对Sprague Dawley大鼠胸主动脉进行体内整合素表达研究。原位杂交显示未损伤主动脉中αv、β3和β5 mRNA信号较低，在14天时显著增加，主要定位于新生内膜。损伤14天后主动脉的Northern分析也显示与未损伤主动脉相比，αv、β3和β5 mRNA上调。与信使水平增加一致，在7天和14天后新生内膜中整合素蛋白表达增加。本研究提供证据表明，在大鼠新生内膜形成过程中αvβ3和αvβ5升高，并表明αvβ5在参与调节平滑肌细胞迁移机制中具有新作用。
