The Effect Of Telmisartan In The Inflammation Of Human Vascular Endothelial Cells Induced With Ages And The Role Of PPAR-γ

[Objctive] To observe the effect of telmisartan on AGEs-induced expre ssion of reactive oxygen species(ROS)and monocyte chemoattractant prot- ein-1 (MCP-1) and the role of PPAR-γin HUVECs.[Methods] Collagenase was used to isolate endothelial cells from human umbilical vein. Gene expression of PPAR-γ,RAGE and MCP-1 was analysed by semiquantitative reverse transcription polymerase chain reaction(RT-PCR)methods.Intracellular formation of ROS was measured using the fluorescent probe DCFH-DA.[Results] Telmisartan(1-1000 nM) downregulated MCP-1 mRNA leveles in a dose-dependent manner,10 nM Telmisartan significantly decreased expression of MCP-1 mRNA (0.963±0.061 vs 1.211±0.039,P﹤0.01)compared with AGEs group.1000 nmol/L Telmisartan upreugulate gene expression of PPAR-γmRNA(0.690±0.170 vs 0.232±0.085, P<0.05)and attenuate the effects induced by AGEs by decrease expression of RAGE mRNA and MCP-1 mRNA (RAGE mRNA:0.385±0.005 vs 0.933±0.039, P<0.01;MCP-1 mRNA:0.590±0.071 vs 1.500±0.160, P<0.01),downregulate the intracellular signal intensity of ROS.GW9662,a specific inhibitor of PPAR-γ,blocked the inhibitor effects of telmisartan on AGEs-induced RAGE and MCP-1 gene exprssion:(RAGE mRNA:0.765±0.032 vs 0.385±0.005, P﹤0.01; MCP-1 mRNA:1.185±0.175 vs 0.590±0.071,P﹤0.01),increase the intracellular signal intensity of ROS and decrease expression of PPAR-γmRNA(0.294±0.020 vs 0.690±0.170,P<0.05).15d-PGJ2,a complete excitomotor of PPAR-γ,increase expression of PPAR-γmRNA ( 0.875±0.112 vs 0.232±0.085,P<0.01)and decrease AGEs-induced intracellular signal intensity of ROS,and downregulate RAGE and subsequent MCP-1 gene induction(RAGE mRNA:0.280±0.020 vs 0.933±0.039,P﹤0.01; MCP-1 mRNA:0.386±0.088 vs 1.500±0.160, P﹤0.01).[Conclusion] Our present study indicates an unique beneficial aspects of telmisartan:it may work as an anti-inflammatory agent against AGEs via PPAR-γactivation in human vascular endothelial cells.