Abstract:AimTo investigate the effects of peroxisome proliferator activated receptor-δ (PPAR-δ) activation by GW0742 on oxidized low density lipoprotein (ox-LDL)induced upregulation of monocyte chemotactic protein-1 (MCP-1),vascular cell adhesion molecule-1 (VCAM-1) and matrix metalloproteinases-9 (MMP-9) in RAW264.7 cells.MethodsCultured RAW264.7 cells were divided into 4 groups: vehicle-treated group,GW0742-treated group, PPAR-δ silencing+GW0742-treated group and empty vector-transformed group.After stimulated with ox-LDL (50 mg/L) for 24 hours,the mRNA and protein levels of MCP-1, VCAM-1 and MMP-9 were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting, respectively.The monocyte migration activity was tested by micropore filter method using a modified Boyden chamber.ResultsBoth the mRNA and protein levels of MCP-1,VCAM-1 and MMP-9 were significantly decreased in GW0742-treated cells compared with vehicle-treated group (P<0.01 or P<0.05 ).However, PPAR-δ gene silencing by RNA interference markedly attenuated these beneficial effects of GW0742 (P<0.01 or P<0.05).Similarly,the monocyte chemotactic activity was noticeably inhibited in GW0742-treated cells (P<0.05),while this inhibitory effect of GW0742 was completely blocked by PPAR-δ gene silencing.ConclusionsThe present study shows that PPAR-δ activation by GW0742 successfully inhibits the oxidized LDL-induced upregulation of MCP-1,VCAM-1 and MMP-9 in RAW264.7 cells and monocyte migration.The results indicates that activating PPAR-δ might become an effective strategy for the prevention of atherosclerosis.