Pannexin1-P2X7 Pathways Mediated Thrombosis Induced By Elabela And Apelin Subtypes

Aim: Elabela and apelin are the endogenous ligand of the G-protein-coupled receptor APJ.Apelin/APJ system is involved in many important physiological and pathological effects,such as adjusting blood pressure,systolic function of heart,glucose homeostasis,immunity,cell proliferation as well as angiogenesis.In this study,we aim to find the function of Elabela and different apelin incuding,apelin-12,apelin-13,apelin-17 and apelin-36 in thrombosis process.And we investgate the role of pannexin1-P2X7 pathway in Elabela,apelin-12,apelin-17,apelin-36,elabela mediated thrombosis;Besides,we also research the importantce of autophagy pathway in apelin-13 mediated the inhibition effect on thrombosis.Overall,these findings indicate new biological function of Elabela and apelin subtypes,which may provide a new theoretical basis and drug screening targets for thrombotic diseases.Methods:1.Thrombosis is detected by rabbit thrombosis detector in vitro.2.The morphology of platelet is observed by HE.3.The plasma level of elabela and apelin subtypes is detected by ELASA in normal and patients of thrombosis desease.Results:1.Elabela or apelin-12,-17,-36 can induce rabbits thrombosis in vitro,while apelin-13 can inhibit rabbits thrombosis induced by ADP in vitro;2.APJ antagonist F13 A can inhibit rabbit thrombosis induced by Elabela or apelin-12,-17,-36 in vitro,and reverse the inhibition effect of apelin-13 on ADP-induced rabbit thrombosis;3.Pannexin-1 antagonist probenecid and carbenoxolone can significantly inhibit rabbit thrombosis induced by Elabela or apelin-12,-17,-36 in vitro,and cann't reverse the inhibition effect of apelin-13 on ADP-induced rabbit thrombosis;4.P2X7 antagonist Brilliant blue G can inhibit rabbit thrombosis induced by Elabela or apelin-12,-17,-36 in vitro;5.Rapamycin of autophagy agonist can block the inhibition effect of apelin-13 on ADP-induced rabbit thrombosis,and 3MA of autophagy inhibitor cann't ehance the inhibition effect of apelin-13 in vitro;6.The expression of Elabela and apelin-12,-17,-36 is decreased in patient's plasma of thrombotic diseases;7.Elabela and apelin-12?apelin-17?apelin-36 induce the activation of platelet,while apelin-13 inhibit ADP-induced platelet activation;Conclusion:Elabela and apelin subtypes apelin-12,-17,-36 induce rabbit thrombosis in vitro,while apelin-13 inhibits rabbit thrombosis induced by ADP in vitro.Moreover,Elabela and apelin-12,-17,-36 induce rabbit thrombosis by pannexin1-P2X7 pathway,while apelin-13 inhibits ADP-induced rabbit thrombosis by inhibiting autophagy pathway.