Troglitazone and rosiglitazone inhibit the low density lipoprotein-induced vascular smooth muscle cell growth

Troglitazone (TRO) and rosiglitazone (RSG) belong to the thiazolidinedione class (insulin-sensitizing agents) and exert many of their metabolic effects as peroxisome proliferator-activated receptor gamma (PPAR gamma) ligands. In the present study we examined the effects of TRO and RSG on LDL-induced VSMC growth. Pretreatment of VSMC with 1 muM TRO or 0.1 muM RSG completely blocked the LDL-induced cell proliferation as measured by [H-3]thymidine incorporation into DNA and by determination of the cell number. We then examined with Western blotting whether these growth suppressing effects are mediated through the mitogen-activated protein kinase (MAPK) pathway, a common signaling pathway activated by growth factors. TRO and RSG had no effect on the LDL-induced stimulation of the MAP kinases ERKK1/2. p38 and SAP/JNK. We conclude that thiazolidinediones are potent inhibitors of LDL-induced VSMC growth acting downstream of the cytoplasmic activation of MAPK.