テルミサルタンはPPARγを介してラット培養血管内皮細胞のPAI-1発現量を減少させる

抄録

Peroxisome proliferators-activated receptor (PPAR)γ was reported to express in vascular endothelial cells (VECs) and was involved in the regulation of coagulation and fibrinolytic system. To examine the effects of PPARγ agonist, troglitazone (TRO) and telmisartan (TMS), on the expression of fibrinolytic and anticoagulant factors, the mRNA expressions of PAI-1, t-PA, u-PA and thrombomodulin (TM) in cultured VECs were measured using the comparative RT-PCR method. Cultured VECs were established from LETO rat's thoracic aorta by the explant method. To determine the concentrations of TRO and TMS used for activation of PPARγ, concentration-dependent activation of PPARγ by TRO and TMS was determined by ELISA measuring binding activity of PPARγ to coactivator (CBP). TRO and TMS concentration-dependently activated PPARγ with the EC₅₀ values of 3.5 μM and 52 μM, respectively. RT-PCR revealed that PPARγ mRNA was constitutively expressed in cultured VECs. The mRNA expression of PAI-1 was significantly decreased by treatment with TMS (50 μM), but not with TRO (10 μM). These result suggest that TMS possibly promotes fibrinolytic activity by downregulation of PAI-1 through PPARγ activation in VECs. [J Physiol Sci. 2008;58 Suppl:S83]