Silencing PCSK9 Protects Vascular Endothelial Cells Function Via SOCS3/JAK/STAT3 Signaling Axis

Objective:This study is mainly to explore the effects of PCSK9 on vascular endothelial cells angiogenesis and the underlying molecular mechanisms of PCSK9 on LPS-induced vascular endothelial cells injury,which provides potential therapeutic targets and help to study the development of arteriosclerosis.Methods:In this research,we take HUVEC-12 as our research object.At first,the effect of LPS on cell viability of HUVEC-12 is detected by CCK-8 assay for finding the best concentration of LPS.After that,we detect the level of PCSK9 mRNA and protein within LPS treatment via QPCR and Western blot.Meanwhile,the transfection efficiency of PCSK9 is determined.Thus,the effect of knocking down PCSK9 and inducing LPS on cell viability of HUVEC-12 is researched and detected by CCK-8 assay.Besides,the effect of knocking out PCSK9 and inducing LPS on angiogenesis ability of HUVEC-12 is also detected by angiogenesis test.In the end,Western blotting is taken advantage to research about the effect of knocking out PCSK9 and inducing LPS on the protein expression of JAK2,p-STAT3,STAT3 and SOCS3.Results:1.LPS treatment upregualtes the level of PCSK9 mRNA and protein in HUVEC-12.2.LPS treatment inhibits the cell viability;while knocking down PCSK9 can alleviate LPS-inducedcell injury.3.LPS suppresses the angiogenesis ability of HUVEC-12,and after knocking down PCSK9,the angiogenesis abilityofHUVEC-12 is recovered.4.LPS treatment induces the activation of JAK/STAT signaling pathway and inhibits the SCOS signal.Whereas,knocking down PCSK9 gene decreases the expression of JAK2 and p-STAT3,but increases the expression of SOCS3,which terminally protects the function of vascular endothelial cells.Conclusion:1.LPS can increase the expression of PCSK9 in HUVEC-12.2.LPS significantly inhibits cell proliferation of HUVEC-12 and decreases angiogenesis of HUVEC-12.3.Knocking down PCSK9 gene significantly promotes the expression of SOCS3,and suppresses the JAK/STAT signaling pathway,which relieves the inhibition of cells viability and improves the dysfunction of angiogenesis ability induced by LPS.