Angiotensin II and PDGF-BB Stimulate β 1 -Integrin–Mediated Adhesion and Spreading in Human VSMCs

—β1 -Integrins play an important role for adhesion and spreading of human smooth muscle cells. In the present study we examined the influence of angiotensin II and platelet-derived growth factor (PDGF)-BB on β1 -integrin–dependent functions of human smooth muscle cells obtained from iliac arteries. Treatment of these cells with PDGF-BB (20 ng/mL) and Angiotensin II (1 μmol/L) did not change β1 -integrin expression up to 48 hours as analyzed by flow cytometry and reverse transcription polymerase chain reaction. β1 -integrins predominantly mediated adhesion of human smooth muscle 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 μmol/L) and 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%, respectively (allP <0.05). Angiotensin II–induced effects were mediated by the AT1 receptor. The PDGF-BB mediated increase of adhesion was inhibited in the presence of genestein, a tyrosine-kinase inhibitor and by protein kinase C downregulation with phorbol 12-myristate 13-acetate. Spreading of smooth muscle cells also was β1 -integrin dependent on collagen I and α5 β1 -integrin dependent on fibronectin. Angiotensin II and PDGF-BB increased cell spreading on fibronectin up to 276% and 318%, respectively, and on collagen I up to 133% and 138% (allP <0.05). These increases were significantly inhibited by blocking antibodies against β1 -integrin, α5 -integrin on fibronectin, the AT1 receptor blocker irbesartan, and genestein. The present data demonstrate that angiotensin II and as well PDGF-BB enhance β1 -integrin–dependent adhesion and spreading of human vascular smooth muscle cells. Furthermore, the experiments with PDGF suggest an involvement of protein kinase C activation leading to these enhanced effects.