Hypoxia and platelet-derived growth factor-BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cells

  • George T. Stavri
  • , Ying Hong
  • , Ian C. Zachary
  • , Georg Breier
  • , Paul A. Baskerville
  • , Seppo Ylä-Herttuala
  • , Werner Risau
  • , John F. Martin*
  • , Jorge D. Erusalimsky
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

167 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) mRNA expression was analysed in rabbit vascular smooth muscle cells following exposure to hypoxia and platelet-derived growth factor-BB (PDGF-BB). Hypoxia potently upregulated VEGF mRNA steady-state levels in a time- and concentration-dependent manner reaching a maximum level (∼30-fold increase) after 12-24 h at 0% 02. In contrast, PDGF-BB caused a modest increase in VEGF expression. However, the combination of PDGF-BB and a threshold hypoxic stimulus (2.5% O2 for 4 h) had a marked synergistic effect. Synergy between hypoxia and PDGF-BB was selective for VEGF expression as hypoxia had no effect on the PDGF-induced upregulation of the proto-oncogene c-myc. These results raise the possibility that hypoxia and PDGF-BB may act in concert to induce VEGF expression in the arterial wall during the development of atherosclerosis.

Original languageEnglish
Pages (from-to)311-315
Number of pages5
JournalFEBS Letters
Volume358
Issue number3
DOIs
Publication statusPublished - 30 Jan 1995
Externally publishedYes

Keywords

  • Atherosclerosis
  • Hypoxia
  • Platelet-derived growth factor
  • Vascular endothelial growth factor
  • Vascular smooth muscle cell

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