INDIRECT ANGIOGENIC CYTOKINES UP-REGULATE VEGF AND BFGF GENE-EXPRESSION IN VASCULAR SMOOTH-MUSCLE CELLS, WHEREAS HYPOXIA UP-REGULATES VEGF EXPRESSION ONLY

Background Hypoxia and indirect angiogenic factors may stimulate angiogenesis via induction of endothelial cell mitogen(s). To evaluate this hypothesis, we investigated whether low oxygen tension or cytokines known to promote neovascularization in vivo could modulate the expression of either vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) in human vascular smooth muscle cells (SMCs). Methods and Results SMCs were treated with platelet-derived growth factor BB (PDGF-BB) or transforming growth factor-beta(1) (TGF-beta(1)) or exposed to low oxygen tension in serum-free medium. Northern analysis detected low basal levels of VEGF and bFGF mRNA in extracts of unstimulated SMCs. However, both VEGF and bFGF transcripts increased after administration of PDGF-BB (10 or 20 ng/mL) or TGF-beta(1) (0.1 to 10 ng/mL). Hypoxia was a potent stimulus for VEGF gene expression but had no apparent effect on bFGF steady-state mRNA levels. Conclusions These results indicate that certain indirect angiogenic cytokines, such as PDGF-BB or TGF-beta(1), may act via induction of bFGF and VEGF gene expression in cells resident near endothelial cells in vivo. Hypoxia constitutes a potent stimulus for VEGF gene expression but does not regulate bFGF under the same experimental conditions.