HYPOXIA AND PLATELET-DERIVED GROWTH FACTOR-BB SYNERGISTICALLY UP-REGULATE 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 reaching a maximum level (similar to 30-fold increase) after 12-24 h at O% O-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.