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(Hypertension. 2000;35:255.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Angiotensin II and PDGF-BB Stimulate ß₁-Integrin–Mediated Adhesion and Spreading in Human VSMCs

Kai Kappert; Gunther Schmidt; Gesine Doerr; Brigitte Wollert-Wulf; Eckart Fleck; Kristof Graf

From the Department of Medicine/Cardiology, Charité, Campus Virchow Klinikum, Humboldt Universität Berlin and Deutsches Herzzentrum Berlin (Germany).

Correspondence to Kristof Graf, MD, Department of Medicine/Cardiology, Charité, Campus Virchow Klinikum and Deutsches Herzzentrum Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. E-mail kristof.graf{at}charite.de

Abstract—ß₁-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 ß₁-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 ß₁-integrin expression up to 48 hours as analyzed by flow cytometry and reverse transcription polymerase chain reaction. ß₁-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 (all P<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 ß₁-integrin dependent on collagen I and ₅ß₁-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<0.05). These increases were significantly inhibited by blocking antibodies against ß₁-integrin, ₅-integrin on fibronectin, the AT₁ receptor blocker irbesartan, and genestein. The present data demonstrate that angiotensin II and as well PDGF-BB enhance ß₁-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.

Key Words: muscle, smooth, vascular • angiotensin II • platelet-derived growth factor

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