Promotion of anoxia-reoxygenation-induced inflammation and permeability enhancement by nicotinamide phosphoribosyltransferase-activated MAPK signaling in human umbilical vein endothelial cells.

Abstract

Previous studies have demonstrated that nicotinamide phosphoribosyltransferase (NAMPT) promoted inflammation and permeability of vascular endothelial cells following cardiopulmonary bypass (CPB). In addition, mitogen-activated protein kinase (MAPK) signaling was activated and contributed to these cell responses. However, the mechanism by which NAMPT regulates cellular inflammation and permeability remains unknown, and whether NAMPT regulates MAPK signaling during this process is also not clear. The present study established an anoxia-reoxygenation (A-R) model using human umbilical vein endothelial cells (HUVECs) and investigated the regulation of MAPK signaling by NAMPT by using small RNA transfection, ELISA and western blot analysis. The results demonstrated that A-R significantly induced the expression levels of NAMPT and cellular permeability-associated proteins, and the release of several inflammatory factors. Furthermore, calcium and MAPK signaling were evidently increased. When the A-R cells were transfected with NAMPT small interfering RNA, the expression of cellular permeability-associated proteins was downregulated, the release of inflammatory factors was decreased, and calcium and MAPK signaling was blocked. These data suggest that NAMPT may activate MAPK signaling to promote A-R-induced inflammation and permeability enhancement of HUVECs. Therefore, the current study indicates that NAMPT may be a potential drug target for A-R-induced endothelial cell injury subsequent to CPB.