Thiazolidinediones inhibit proliferation of microvascular and macrovascular cells by a PPAR?-independent mechanism

This study evaluated the hypothesis that peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists, including thiazolidinediones (TZDs) and the rexinoid LG100268 (LG), directly affect human vascular cell function (proliferation, cell cycle, protein expression, lactate release) independently of (1) their PPARgamma-activating potential and (2) the cells' vascular origin. Human umbilical vein endothelial cells (HUVECs), human adult vein endothelial cells (HAVECs), human retinal endothelial cells (HRECs) and human retinal pericytes (HRPYCs) were incubated (48 h) with 2-50 micromol/l rosiglitazone (RSG), RWJ241947 (RWJ), pioglitazone (PIO), troglitazone (TRO), 15-deoxy-Delta(12,14)-prostaglandin J2 (PGJ2) and LG. Proliferation, cell cycle distribution, protein expression, peroxisome proliferator-activated receptor responsive element (PPRE) transcriptional activity and mitochondrial effects were determined by [3H]thymidine incorporation, FACS analyses, western blots, reporter assays and lactate release respectively. In HUVECs, RSG, RWJ, PIO, TRO, PGJ2 and LG reduced (p