Angiotensin II and PDGF-BB stimulate beta(1)-integrin-mediated adhesion and spreading in human VSMCs

beta(1)-Integrins play an important role for adhesion and spreading of huma n smooth muscle cells. In the present study we examined the influence of an giotensin II and platelet-derived growth factor (PDGF)-BB on beta(1)-integr in-dependent functions of human smooth muscle cells obtained from iliac art eries. Treatment of these cells with PDGF-BB (20 ng/mL) and Angiotensin II (1 mu mol/L) did not change beta(1)-integrin expression up to 48 hours as a nalyzed by flow cytometry and reverse transcription polymerase chain reacti on. beta(1)-integrins predominantly mediated adhesion of human smooth muscl e cells to collagen I (79.7+/-4.4%, P<0.01) and fibronectin (66.6+/-2.4%, P <0.01). Treatment of smooth muscle cells with Angiotensin II (1 mu mol/L) a nd PDGF-BB (20 ng/mL) significantly increased the adhesion to collagen I by 56.5% and 44.3%, respectively, and to fibronectin by 49.6% and 36.4%, resp ectively (all P<0.05). Angiotensin II-induced effects were mediated by the AT(1) receptor. The PDGF-BB mediated increase of adhesion was inhibited in the presence of genestein, a tyrosine-kinase inhibitor and by protein kinas e C downregulation with phorbol 12-myristate 13-acetate. Spreading of smoot h muscle cells also was beta(1)-integrin dependent on collagen I and alpha( 5)beta(1)-integrin dependent on fibronectin. Angiotensin II and PDGF-BB inc reased cell spreading on fibronectin up to 276% and 318%, respectively, and on collagen I up to 133% and 138% (all P<0.05). These increases were signi ficantly inhibited by blocking antibodies against beta(1)-integrin, alpha(5 )-integrin on fibronectin, the AT(1) receptor blocker irbesartan, and genes tein. The present data demonstrate that angiotensin II and as well PDGF-BB enhance beta(1)-integrin-dependent adhesion and spreading of human vascular smooth muscle cells. Furthermore, the experiments with PDGF suggest an inv olvement of protein kinase C activation leading to these enhanced effects.