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

Abstract

—β ₁ -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 β ₁ -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 β ₁ -integrin expression up to 48 hours as analyzed by flow cytometry and reverse transcription polymerase chain reaction. β ₁ -integrins predominantly mediated adhesion of human smooth muscle cells to collagen I (79.7±4.4%, P P P 1 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 β ₁ -integrin dependent on collagen I and α ₅ β ₁ -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% (all P 1 -integrin, α ₅ -integrin on fibronectin, the AT ₁ receptor blocker irbesartan, and genestein. The present data demonstrate that angiotensin II and as well PDGF-BB enhance β ₁ -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.