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

Hypertension. 2000 Jan;35(1 Pt 2):255-61. doi: 10.1161/01.hyp.35.1.255.

Abstract

beta(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 beta(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 micromol/L) did not change beta(1)-integrin expression up to 48 hours as analyzed by flow cytometry and reverse transcription polymerase chain reaction. beta(1)-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 micromol/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 AT(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 beta(1)-integrin dependent on collagen I and alpha(5)beta(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<0.05). These increases were significantly inhibited by blocking antibodies against beta(1)-integrin, alpha(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 beta(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Anticoagulants / pharmacology*
  • Antigens, CD / genetics
  • Antihypertensive Agents / pharmacology
  • Aorta / cytology
  • Becaplermin
  • Biphenyl Compounds / pharmacology
  • Carcinogens / pharmacology
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Collagen / pharmacology
  • Culture Techniques
  • Enzyme Inhibitors / pharmacology
  • Fibronectins / pharmacology
  • Flow Cytometry
  • Gene Expression / drug effects
  • Genistein / pharmacology
  • Humans
  • Iliac Artery / cytology
  • Imidazoles / pharmacology
  • Integrin alpha5
  • Integrin beta1 / genetics
  • Irbesartan
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects*
  • Platelet-Derived Growth Factor / pharmacology*
  • Proto-Oncogene Proteins c-sis
  • Pyridines / pharmacology
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tetrazoles / pharmacology
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Anticoagulants
  • Antigens, CD
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Carcinogens
  • Enzyme Inhibitors
  • Fibronectins
  • Imidazoles
  • Integrin alpha5
  • Integrin beta1
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Pyridines
  • RNA, Messenger
  • Tetrazoles
  • Vasoconstrictor Agents
  • Angiotensin II
  • PD 123319
  • Becaplermin
  • Collagen
  • Genistein
  • Irbesartan
  • Tetradecanoylphorbol Acetate