Effect And Mechanism Of Peroxisome Proliferator Activated Receptorδ On The MCP-1、VCAM-1mRNA Expression Induced By Homocysteine In Cultured Human Endothelial Cells

AIM:Atherosclerosis(AS) is an chronic inflammatory disease of cardiovascularsystem. Monocyte chemoattractant protein-1（MCP-1）, vascular cess adhesionmolecule-1（VCAM-1） are significant pro-inflammatory factors in the wholepathological process of AS. Hyperhomocysteinemia（HHcy）has been recognized asan independent risk factor for cardiovascular. Peroxisome proliferator activatedreceptor δ (PPARδ) is a family of nuclear receptors, which have many biologicalroles. In this study, we investigate the effect and mechanism of PPARδ on theMCP-1,VCAM-1mRNA expression induced by homocysteine (Hcy) in humanumbilical vein endothelial cells(HUVECs).METHODS:Collagenase was used to isolate endothelial cells from human umbilical vein,and the cells was cultured in vitro. Experimental Group: Blank control group; Hcygroup; GW0742(the specific agonists of PPARδ) group; GSK0660(the specificinhibitors of PPARδ) group; PDTC(the specific inhibitors of NF-κB) group; DPI(thespecific inhibitors of NADPH oxidase) group. RT-PCR was used to examine theexpression of MCP-1,VCAM-1mRNA; Western-blotting was used to detect the levelon unclear, cytosolic and total NF-κB p65and PPARδ protein; DCFH-DA was addedto monitor intracellular reactive oxygen species(ROS) production.RESULTS:①HUVECs were cultured in vitro and definited as HUVECs using morphologyand immunofluorescence.②Hcy promoted the expression of MCP-1,VCAM-1mRNA in a concentration dependent manner in vascular endothelium, and the expression of MCP-1,VCAM-1mRNA was elevated significantly by Hcy (10μM)(P0.05).③Levels of MCP-1,VCAM-1mRNA increased by Hcy were significantlyattenuated by pretreatment with GW0742and PDTC (P0.05).④The NF-κB p65protein level of unclear extracts increased by Hcy wasprevented by GW0742and DPI(P0.05).⑤The Hcy-induced production of ROS was significantly attenuated by GW0742(P0.05).⑥The PPARδ protein level decreased by Hcy was prevented by GW0742(P0.05).CONCLUSION:①Hcy increased the expression of MCP-1, VCAM-1mRNA in vascularendothelium.②The activation of PPARδ decreased the expression of MCP-1, VCAM-1,mRNA induced by Hcy in vascular endothelium, possibly by suppressing theactivation of ROS/NF-κB pathway.