6-Shogaol Suppresses Vsmc Migration And Proliferation Via Inhibiting TLR4/NF-?B Pathway

Objective and backgrand:Atherosclerosis is the major cause of ischemic heart disease,stroke,and peripheral vascular disease.Intimal hyperplasia is the key process of early pathological,and VSMC migration and proliferation have considered to be the major cause of IH..Therefore,Suppression of VSMC proliferation appears to be an important strategy for the prevention of IH and vascular restenosisToll like receptors(TLRs)are highly conserved transmembrane protein receptors that mediating innate immunity.Toll like receptor 4,a member of TLRs family,wildly expressed on cardiomyocytes,airway epithelial,adipose tissue,macrophages,skeletal muscle and vascular endothelial and smooth muscle cells.Recently,increasing evidence suggests that TLR4-mediated inflammation plays an essential role in VSMCs proliferation and neointimal formation,VSMCs proliferation can be reduced by down-regulate the expression of TLR4.6-shogaol,a major active component in ginger,can inhibit the Pancreatic Cancer cells proliferation through modulate the TLR4/NF-? B pathway[12].We presume that 6-shogaol can inhibit VSMCs proliferation by down-regulate of TLR4/ NF-?B pathway.Methods1.VSMCs were isolated from the thoracic aorta of Wild type(WT,C57BL/6J background)and TLR4-/-(C57BL/6J background)mice using an explant technique.2.TLR4??-actin and NF-?B was detected by Western Blot.3.The MTT assay was used to detect the cell proliferation,and the cell migration was examined using transwell.Results1.The WT and TLR4-/-VSMC was obtained.2.PDGF and LPS induced the expression of TLR4 and the migration and proliferation of VSMCs(P<0.05),the migration and proliferation of VSMC can be inhabited by reduce the expression of TLR4(P<0.05);3.6-shogaol inhabit the proliferation and migration of VSMCs(P<0.05);4.6-shogaol inhabit the expression of TLR4(P<0.05);6-shogaol inhabit the expression of NF-?B(P<0.05).Conclusion6-shogaol suppresses VSMC proliferation via inhibiting TLR4/NF-?B pathway.