Peroxisome Proliferator-Activated Receptor γ Ligands Retard Cultured Vascular Smooth Muscle Cells Calcification Induced by High Glucose

Peroxisome proliferator-activated receptor gamma (PPAR gamma) and its ligands have profound effects on glucose homeostasis, cardiovascular diseases, and bone metabolism. To explore the pathophysiological roles of PPAR gamma in diabetes with concomitant vascular calcification, we investigated changes in PPAR gamma expression and the effect of the PPAR gamma ligands troglitazone and rosiglitazone on vascular smooth muscle cell (VSMC) calcification induced by high glucose (HG, 25 mmol/L). Compared with low glucose, HG-induced VSMC calcification, and PPAR gamma mRNA, protein level was decreased. Troglitazone and rosiglitazone treatment markedly attenuated the VSMC calcification, whereas PPAR gamma antagonist GW9662 abolished the effect of rosiglitazone on calcification. Pretreatment of VSMCs with rosiglitazone, but not troglitazone, restored the loss of lineage marker expression: the protein levels of alpha-actin and SM-22 alpha were increased 52 % (P < 0.05) and 53.1 % (P < 0.01), respectively, as compared with HG alone. Troglitazone and rosiglitazone reversed the change in bone-related protein expression induced by HG: decreased the mRNA levels of osteocalcin, bone morphogenetic protein 2 (BMP2), and core binding factor alpha 1 (Cbf alpha-1) by 26.9 % (P > 0.05), 50.0 % (P < 0.01), and 24.4 % (P < 0.05), and 48.4 % (P < 0.05), 41.4 % (P < 0.01) and 56.2 % (P < 0.05), respectively, and increased that of matrix Gla protein (MGP) 84.2 % (P < 0.01) and 70.0 %, respectively (P < 0.05), as compared with HG alone. GW9662 abolished the effect of rosiglitazone on Cbf alpha-1 and MGP expression. PPAR gamma ligands can inhibit VSMCs calcification induced by high glucose.