Peroxisome proliferator-activated receptor γ ligands retard cultured vascular smooth muscle cells calcification induced by high glucose.

Peroxisome proliferator-activated receptor γ (PPARγ) and its ligands have profound effects on glucose homeostasis, cardiovascular diseases, and bone metabolism. To explore the pathophysiological roles of PPARγ in diabetes with concomitant vascular calcification, we investigated changes in PPARγ expression and the effect of the PPARγ 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 PPARγ mRNA, protein level was decreased. Troglitazone and rosiglitazone treatment markedly attenuated the VSMC calcification, whereas PPARγ 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 α-actin and SM-22α 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 α 1 (Cbfα-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 Cbfα-1 and MGP expression. PPARγ ligands can inhibit VSMCs calcification induced by high glucose.