IL-33 / ST2 Signaling Promotes TF Expression by Regulating NF-κB Activation in Coronary Artery Endothelial Microparticles of Acute Myocardial Infarction

Abstract Background: Interleukin (IL)-33 was previously shown to induce angiogenesis and inflammatory activation of endothelial cells derived Microparticles（EMPs）. Tissue factor (TF) plays a central role in hemostasis and thrombosis. Objective: The aim of this study was to investigate the effect of IL-33 on TF release of EMPs, which may be a new link between inflammation and coagulation. Methods: The study analyzed the coronary blood of level of CD31+EMPs, TF protein and IL-33 protein in acute myocardial infarction(AMI) and stable coronary artery disease(SCAD) patients. Human coronary artery endothelial cells (HCAECs) were treated with IL-33 to obtain MPs. The TF activity of EMPs was tested by thermo fisher by adding the TF antibody. Furthermore, TF and TFPI protein were tested by ELISA. Finally, NF-κB inhibitor dimethyl fumarate (DMF) and soluble extracellular domain of ST2 coupled to the Fc fragment of human IgG1 (sST2) were added HCAECs, which were treated with IL-33, then the TF protein level also was tested by ELISA. Results: The AMI patients have higher level of CD31+EMPs, TF protein and IL-33 protein than the SCAD patients in coronary blood. In AMI patients (N=27) , the IL-33 protein positively correlated with CD31+EMPs (r = 0.794, p < 0.01). According to the ROC curve analysis, the areas under the curve (AUC) of CD31+EMPs, TF protein and IL-33 protein were 0.888, 0.962 and 0.778. In the cell culture, the TF activity and TF protein in ECs-derived MPs increased gradually with time of intervention by the treatment of IL-33. IL-33 binding to the ST2 receptor promoted TF expression by regulating NF-κB activation in ECs-derived MPs of HCAECs. Conclusion: Activated endothelial cells and their released MPs simultaneously express TF, which is a risk factor for cardiovascular disease.