title: Activation of the integrins alpha 5beta 1 and alpha v beta 3 and focal adhesion kinase (FAK) during arteriogenesis.
abstract: Migration and proliferation of smooth muscle cells (SMC) are important events during arteriogenesis, but the underlying mechanism is still only partially understood. The present study investigates the expression of integrins alpha 5 beta 1 and v beta 3 as well as focal adhesion kinase (FAK) and phosphorylated FAK (pY397), key mediators for cell migration and proliferation, in collateral vessels (CV) in rabbit hind limbs induced by femoral ligation or an arteriovenous (AV) shunt created between the distal femoral artery stump and the accompanying femoral vein by confocal immunofluorescence. In addition, the effect of the extracellular matrix components fibronectin (FN), laminin (LN), and Matrigel on expression of these focal adhesion molecules proliferation was studied in cultured SMCs. We found that: (1) in normal vessels (NV), both integrins alpha 5 beta 1 and alpha v beta 3 were mainly expressed in endothelial cells, very weak in smooth muscle cells (SMC); (2) in CVs, both alpha 5 beta 1 and alpha v beta 3 were significantly upregulated (P < 0.05); this was more evident in the shunt-side CVs, 1.5 and 1.3 times higher than that in the ligation side, respectively; (3) FAK and FAK(py397) were expressed in NVs and CVs in a similar profile as was alpha 5 beta 1 and alpha v beta 3; (4) in vitro SMCs cultured on fibronectin (overexpressed in collaterals) expressed higher levels of FAK, FAK (pY397), alpha 5 beta 1, and alpha v beta 3 than on laminin, whereas SMCs growing inside Matrigel expressed little of these proteins and showed no proliferation. In conclusion, our data demonstrate for the first time that the integrin-FAK signaling axis is activated in collateral vessels and that altered expression of FN and LN may play a crucial role in mediating the integrin-FAK signaling pathway activation. These findings explain a large part of the positive remodeling that collateral vessels undergo under the influence of high fluid shear stress.
authors.affiliation: Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, 172 Tong-Zhi-Po Road, Changsha, 410078, Hunan, People's Republic of China. wjcai@yahoo.com
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Cai
authors.forename: Ming Bo
authors.initials: MB
authors.lastname: Li
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Wu
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.forename: Wu
authors.initials: W
authors.lastname: Zhu
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Mingying
authors.initials: M
authors.lastname: Luo
authors.forename: Inka
authors.initials: I
authors.lastname: Eitenmüller
authors.forename: Andreas
authors.initials: A
authors.lastname: Kampmann
authors.forename: Jutta
authors.initials: J
authors.lastname: Schaper
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaper
mesh_terms: D000818:Animals; D001158:Arteries / Q000254:growth & development / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005263:Femoral Artery / Q000166:cytology / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D007150:Immunohistochemistry; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008854:Microscopy, Electron; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D011817:Rabbits; D020257:Ventricular Remodeling
chemical_list: D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D051416:Focal Adhesion Protein-Tyrosine Kinases