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Polyamine Synthesis Inhibition Attenuates Vascular Smooth Muscle Cell Migration.

Author

Summary, in English

Vascular smooth muscle cell migration, occurring after intimal injury, is a substantial clinical problem in atherosclerosis and restenosis after stenting. Here we investigate the effects of polyamine synthesis inhibition on vascular smooth muscle cell migration after maximal and submaximal growth stimulation with PDGF-AB or FCS. Vascular smooth muscle cells were obtained from mouse aorta explants. These cells coexpressed smooth muscle alpha-actin, PDGFRalpha and PDGFRbeta as demonstrated by immunocytochemistry. Treatment with a high (100 ng/ ml) concentration of PDGF-AB stimulated DNA synthesis 6-fold and markedly elevated cell migration. PDGF-AB (100 ng/ml) increased cellular spermidine concentration 2-fold, but had no effect on spermine or putrescine levels. Treatment with the polyamine synthesis inhibitors CGP48664 (1 µM) and DFMO (5 mM) prevented the PDGF-AB-induced increase in spermidine and reduced spermine concentrations, but had no effect on PDGF-AB-stimulated DNA synthesis or cell migration. Cell migration after submaximal stimulation with either PDGF-AB (8 ng/ml) or FCS (8%) was, however, inhibited by the polyamine synthesis blockers. In summary, these data show that polyamine synthesis inhibition attenuates vascular smooth muscle cell migration under submaximal growth-stimulating conditions, suggesting that polyamines participate in regulation of cell migration and that treatment with polyamine synthesis inhibitors might reduce vascular smooth muscle cell migration after intimal injury.

Department/s

Publishing year

2004

Language

English

Pages

141-147

Publication/Series

Journal of Vascular Research

Volume

41

Issue

2

Document type

Journal article

Publisher

Karger

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • Cell migration
  • FCS
  • PDGF-AB
  • Polyamines
  • Vascular smooth muscle cells

Status

Published

Research group

  • Vascular Physiology
  • Neurogastroenterology

ISBN/ISSN/Other

  • ISSN: 1423-0135