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  • Title: Hypoxia and platelet-derived growth factor-BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cells.
    Author: Stavri GT, Hong Y, Zachary IC, Breier G, Baskerville PA, Ylä-Herttuala S, Risau W, Martin JF, Erusalimsky JD.
    Journal: FEBS Lett; 1995 Jan 30; 358(3):311-5. PubMed ID: 7843420.
    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 (approximately 30-fold increase) after 12-24 h at 0% 0(2). 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.
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