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

Autor: Kappert, Kai, Blaschke, Florian, Meehan, Woerner P., Kawano, Hiroaki, Grill, Matthias, Fleck, Eckart, Hsueh, Willa A., Law, Ronald E., Graf, Kristof
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Zdroj: Basic Research in Cardiology; Jan2001, Vol. 96 Issue 1, p42-49, 8p
Abstrakt: Neointima formation involves tissue expression of matrix proteins and growth factors. The role of αvβ3, but not αvβ5 integrin in vascular cells has been sufficiently investigated. The aim of the present study was to determine and compare the function of αvβ3 and αvβ5 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 αvβ3 and αvβ5 integrin subunits. The αvβ5 integrin predominantly mediated adhesion of RASMCs to vitronectin and spreading on vitronectin via RGD-binding sequences. In contrast, the αvβ3 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 αvβ3 and αvβ5 integrins. Selective blocking antibodies for αvβ3 and αvβ5 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 αvβ3 and β5 mRNA in uninjuried 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 αvβ3 and β5 mRNA compared to uninjured aorta. Consistent with the increase in message levels, increased inegrin protein expression was seen in the neointima after 7 and 14 days. This study provides evidence that αvβ3 and αvβ5 are elevated during neointima formation in the rat and indicates a novel role for αvβ5 participating in mechanisms regulating smooth muscle cell migration. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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