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

FEBS Letters

Ylä-Herttuala, Seppo²  Hong, Ying¹  Baskerville, Paul A.¹  Breier, Georg³  Martin, John F.¹  Stavri, George T.¹  Risau, Werner³  Zachary, Ian C.¹  Erusalimsky, Jorge D.¹ 

[1] Department of Medicine and Department of Surgery, King's College School of Medicine and Dentistry, Besssemer Road, London, SE5 9PJ, UK;Department of Biomedical Sciences, University of Tampere, 33101 Tampere, Finland;Department of Molecular Cell Biology, Max-Planck-Institut fur physiologische und klinische Forschung, W. G. Kerckhoff Institut, 61231, Bad Nauheim, Germany

关键词: Hypoxia;    Vascular endothelial growth factor;    Platelet-derived growth factor;    Vascular smooth muscle cell;    Atherosclerosis;   

DOI  :  10.1016/0014-5793(94)01458-D

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown