The Effects Of Ticagrelor On PCSK9, Inflammation Factor Expression And Their Relations In Apoptosis Of Human Umbilical Vein Endothelial Cells Induced By Ox-LDL

ObjectiveTo investigate the effects of Ticagrelor on proprotein convertase subtilisin/kexin type 9(PCSK9), inflammation factor expression and their relations in apoptosis of Human Umbilical Vein Endothelial Cells induced by oxidized low density lipoprotein(ox-LDL).MethodsHUVECs were incubated with 50μg/ml ox-LDL for different times(0h, 12 h, 24 h, 36 h, 48h). RT-PCR was conducted to detect the mRNA level of PCSK9, inter leukin 6(IL-6), monocyte chemotactic protein-1(MCP-1), matrix metalloprotein-9(MMP-9), c-reactive protein(CRP), and the nucler displacement of nucler factor-kappa B(NF-κB). ELISA was used to analysis the protein level of IL-6, MCP-1, MMP-9 and CRP. The PCSK9 siRNA were designed and synthesized, and then were transfected 100nmol/L into HUVECs by Lipofectamine 2000. After transfection for 6h, cells were treated with 50μg/ml ox-LDL for 24 h. RT-PCR was conducted to detect the mRNA level of PCSK9, IL-6, MCP-1, MMP-9, CRP, and the nuclear displacement of NF-κB. ELISA was used to analysis the protein level of IL-6, MCP-1, MMP-9 and CRP. HUVECs were treated with 50μg/ml ox-LDL and different concentrations of Ticagrelor(40, 60μmol/L) for 24 h. RT-PCR was conducted to detect the mRNA level of PCSK9, IL-6, MCP-1, MMP-9, CRP, and the nuclear displacement of NF-κB. ELISA was used to analysis the protein level of IL-6, MCP-1, MMP-9 and CRP.ResultsWithin a certain period of time, the expression of the mRNA and protein level of PCSK9, IL-6, MCP-1, MMP-9, CRP, and the nuclear displacement of NF-κB increased gadually with the increase of time of ox-LDL in the treatment of HUVECs. The expression of the mRNA and protein level of PCSK9, IL-6, MCP-1, MMP-9, CRP, and the nuclear displacement of NF-κB in siRNA group was significantly lower than that in negative transfection(NC) group(P<0.05). Ticagrelor can significantly reduce the expression of the mRNA and protein level of PCSK9, IL-6, MCP-1, MMP-9, CRP, and the nuclear displacement of NF-κB, which is concentration dependent(P<0.05).ConclusionThere is the expression of PCSK9 in apoptosis of HUVECs induced by ox-LDL. The expression of PCSK9 and the concentration of inflammatory factors are related to the degree of HUVECs apoptosis. PCSK9 siRNA can repress the expression of inflammation factor in HUVECs, which is induced by ox-LDL. PCSK9 may be involved in adjustment for inflammation. Ticagrelor can repress the expression of PCSK9 and inflammation factor in HUVECs, which is induced by ox-LDL. The mechanism of Ticagrelor anti-inflammatory may have a relationship with the mechanism of it repress the expression of PCSK9.