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

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 reachi...

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Bibliographic Details
Published in:FEBS letters 1995-01, Vol.358 (3), p.311-315
Main Authors: Stavri, George T., Hong, Ying, Zachary, Ian C., Breier, Georg, Baskerville, Paul A., Ylä-Herttuala, Seppo, Risau, Werner, Martin, John F., Erusalimsky, Jorge D.
Format: Article
Language:English
Subjects:
Atherosclerosis
Base Sequence
Becaplermin
Cell Hypoxia
Cells, Cultured
DNA, Complementary
Endothelial Growth Factors - biosynthesis
Endothelial Growth Factors - genetics
Gene Expression Regulation
Humans
Hypoxia
Lymphokines - biosynthesis
Lymphokines - genetics
Molecular Sequence Data
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - metabolism
Platelet-derived growth factor
Platelet-Derived Growth Factor - physiology
Proto-Oncogene Proteins c-sis
Recombinant Proteins
RNA, Messenger - genetics
RNA, Messenger - metabolism
Up-Regulation
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Vascular smooth muscle cell
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Summary: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% 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% O 2 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.
ISSN:0014-5793
1873-3468
DOI:10.1016/0014-5793(94)01458-D