Peroxisome proliferator-activated receptor-gamma agonists increase vascular endothelial growth factor expression in human vascular smooth muscle cells

Vascular endothelial growth factor (VEGF), expressed in a variety of mesenc hymal cells including vascular smooth muscle cells (VSMC), is a potent mito gen for endothelial cells, and is used clinically applied for ischemic dise ase of peripheral vessels. To determine whether peroxisome proliferator-act ivated receptor gamma (PPAR gamma) regulates VEGF production in VSMC, we ex amined VEGF secretion from VSMC treated with PPAR agonists. Troglitazone in creased VEGF secretion in a time- and dose-dependent manner (261 +/- 35% wi th 25 mM of troglitazone for 24 h), and also increased levels of VEGF mRNA. VEGF secretion was also increased by other PPAR gamma agonists, pioglitazo ne, LY171883, and 15d-PGJ2 (224 +/- 17.1%, 247 +/- 36.8% and 171 +/- 7.8%, respectively), but not the PPAR gamma agonists bezafibrate and Wy14643 (85. 2 +/- 1.5%, 94.6 +/- 3.2, respectively). Our findings suggest that thiazoli dinediones might be useful for the therapeutic angiogenesis for ischemic ar tery disease. (C) 2000 Academic Press.