Pd-Ia Inhibits Inflammatory Response Induced By LPS In HUVECs Via PPAR? Signal Pathway

Objective:Atherosclerosis as the main pathological basis of coronary heart disease,stroke and other ischemic cardio-cerebrovascular diseases,controlling its development is the fundamental strategic measures for the prevention of the cardiovascular and cerebrovascular diseases.Researches show that atherosclerosis is a kind of chronic inflammation of the vessel walls,and vascular endothelial cell injury is the key factor of atherosclerosis.Damaged endothelial cells will produce excessive inflammatory mediators,which can promote monocyte adhesion,aggregation and activation,and start atherosclerosis.Pd-Ia is a novel Ca²⁺-influx blocker and K⁺-channel opener.It has been proved to have anti-apoptotic and anti-inflammatory action in ischemia/reperfusion myocardiocytes.Peroxidase body growth activated receptor?PPAR alpha?as a member of the nuclear receptor superfamily can inhibit the nf-kappa B and AP-1 signaling pathway to fight inflammation.Our preliminary experimental results show that Pd-Ia can inhibit Lipopolysaccharide-induced inflammatory response in Human Umbilical Vein Endothelial Cells.This topic mainly investigates whether Pd-Ia inhibits inflammatory response induced by LPS via PPARa signal pathway in HUVECs.Methods:HUVECs were treated with 1?g/mL LPS and different concentrations of Pd-Ia?10,20,40 ?M?.Real-time PCR was performed to measure the effects of Pd-Ia on the expression of Icam,Vcam,E-selectin,MCP-1,MCP-2.Immunofluorescence and Western blot were performed to measure the effects of Pd-Ia on the distribution and expression of PPARa and NF-?B,By using the methods of siRNA and drug blocking PPARa pathway to clear the effect of PPARa on Pd-Ia regulating NF-?B signal pathway.By using the methods of drug blocking PKA to discuss the effect of Pd-Ia on PPARa.Results:1.Pd-Ia can down-regulate the expression of MCP-2 and Vcam.2.Pd-Ia can regulate NF-?B signal pathway via PPARa.3.Pd-Ia can regulate the activity of PPARa via activating PKA.4.Pd-Ia also inhibits inflammatory response via P38,ERK signal pathways.Conclution:Pd-Ia can inhibit inflammatory response induced by LPS in HUVECs via PPARa/NF-KB signal pathways.And Pd-Ia regulates the activity of PPARa via PKA signal pathway.The study results suggest Pd-Ia is expected to become a potential drug for the treatment of atherosclerosis disease.