Orexin A Suppresses Oxidized LDL Induced Endothelial Cell Inflammation via MAPK p38 and NF-κB Signaling Pathway

Abstract

Orexin A is a multifaceted peptide produced in hypothalamus. We examined the effect of orexin A on vascular endothelial cells. Our study showed that orexin A had a profound inhibitory effect against endothelial inflammation by oxidized low-density lipoprotein (ox-LDL) in endothelial cells. Orexin A partially suppressed ox-LDL-induced monocytes THP-1 cells attachment to endothelial cells by limiting expression of vascular molecules including VCAM-1, ICAM-1, and E-selectin. Mechanistically, orexin A ameliorated endothelial dysfunction by reducing MAP kinase p38 and NF-κB activation via its receptor-OX1R. Orexin A suppressed phosphorylation of MAP kinase p38 and the NF-κB cascade kinases IKKα and IκBα, and prevented the shuttle of p65 protein into nuclear. Additionally, we reported that OX1R was expressed in HUVECs. Silence of OX1R completely abolished the inhibitory function of orexin in attachment of THP-1 cells. Collectively, our data suggest that orexin A ameliorated endothelial dysfunction under inflammatory stimuli. © 2018 IUBMB Life, 70(10):961–968, 2018.