Ligands of peroxisome proliferator-activated receptor-γ increase the generation of vascular endothelial growth factor in vascular smooth muscle cells and in macrophages

Peroxisome proliferator-activated receptors-gamma (PPAR gamma) are ligand-inducible transcription factors of the nuclear hormone receptor superfamily. We examined the effect of PPAR gamma activation on the generation of vascular endothelial growth factor (VEGF), one of the major angiogenic agents. Rat vascular smooth muscle cells (VSMC) and murine macrophages RAW264.7 were incubated for 24 h with PPAR gamma activators: prostaglandin J(2) and ciglitazone. PPAR gamma were expressed in VSMC and RAW cells and their activity was upregulated in the presence of PGJ(2) and ciglitazone. Incubation of the cells with PPAR gamma activators significantly augmented the release of VEGF protein into the media, both in resting and in IL-1 beta- or LPS-stimulated cultures. The higher protein generation was connected with the increased expression of mRNA and transcriptional activation of VEGF promoter. We conclude that the activation of PPAR gamma upregulates the generation of VEGF and may be involved in the regulation of angiogenesis.