Ticagrelor and clopidogrel suppress NF-κB signaling pathway to alleviate LPS-induced dysfunction in vein endothelial cells

Background: Ticagrelor and clopidogrel, P2Y(12) receptor antagonists, can prevent thrombotic events and are used to treat cardiovascular diseases such as acute coronary syndrome and chronic obstructive pulmonary disease, in which inflammation is involved. Moreover, NF-B is the central regulator of inflammation. Thus, we suspected that ticagrelor and clopidogrel are involved in the regulation of the NF-kappa B signaling pathway. Methods: After human umbilical vein endothelial cells (HUVECs) were cultured with ticagrelor or clopidogrel and given lipopolysaccharide (LPS) and CD14, the mRNA levels of related inflammatory factors, the protein level and subcellular localization of molecules in the NF-kappa B signaling pathway, cell viability, apoptosis and the cell cycle, cell migration, and vascular formation were detected using quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence assay, CCK-8, flow cytometry, transwell assay, and matrigel, respectively. All data was expressed as the mean +/- S.D. The statistical significance of data was assessed by an unpaired two-tailed t-test. Results: Ticagrelor and clopidogrel can inhibit the degradation of IKB alpha and phosphorylation of p65, prevent p65 from entering the nucleus, reduce the production of TNF alpha, IL-1, IL-8, IL-6 and IL-2, and alleviate the decrease in cell viability, cell migration and angiogenesis, the changes of cell cycle and apoptosis induced by LPS. Conclusions: Ticagrelor and clopidogrel alleviate cellular dysfunction through suppressing NF-kappa B signaling pathway.