The involvement of protein TNFSF18 in promoting p-STAT1 phosphorylation to induce coronary microcirculation disturbance in atherosclerotic mouse model

The inflammation of coronary endothelium was critically involved in the pathogenesis of atherosclerosis. The purpose of the study was to reveal the roles of TNFSF18 in promoting p-STAT1 phosphorylation to induce disturbance of coronary microcirculation in atherosclerotic mouse model. This study was dividedly transfected TNFSF18 inhibitor, small interfering-TNFSF18 plasmid (si-TNFSF18) and a blank vector plasmid into atherosclerotic mouse model. Results showed that the coronary vascular lumen was narrowed and crescent plaques were adhered to the coronary vessel wall in atherosclerotic mouse model. However, the accumulation of microthrombus in coronary artery and vascular crescent plaques were evidently reduced with the antagonistic TNFSF18. Besides, the inflammatory cytokines TNF-α, TNF-β and IL-1β were abundant in mouse model, and TNFSF18 inhibition decreased the secretion of cytokines. Meanwhile, the amount of Th1 cells were also reduced after transfected with TNFSF18 inhibitor and si-TNFSF18 plasmid compared with the mouse model transfected with blank vector plasmid. Moreover, the protein TNFSF18 was highly expressed in the cytoplasm and p-STAT1 was located in cell nucleus of the mouse model coronary vascular tissues. Consistently, the proteins TNFSF18, p-STAT1, VCAM1, ICAM1, ITGAD and ITGB3 were significantly expressed in atherosclerotic mouse model, while antagonistic TNFSF18, conversely, decreased the proteins' expression. Taken together, this study indicated that the coronary endothelial inflammation triggered TNFSF18 expression, which promoted p-STAT1 phosphorylation to activate the proteins VCAM1, ICAM1, ITGAD and ITGB3, thus exacerbating coronary microcirculation disorder in atherosclerotic mouse model.

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