Phoenixin-20 Prevents ox-LDL-Induced Attachment of Monocytes to Human Aortic Endothelial Cells (HAECs): A Protective Implication in Atherosclerosis
Xiaolan Wei, Huasong Lin, Biyue Zhang, Mimi Li, Ya‐Fang Chen, Yali Huang, Jinying Zhang, Yingxia Yang, Zeming Guo, Weiwei Li, Lichao Ye, Ruoting Lin
Abstract
The exact cause of atherosclerosis is not known, and therefore, the current treatment options are limited. The activation of endothelial cells by oxidized low-density lipoprotein (ox-LDL) plays a key role in the initiation and progression of atherosclerosis. Phoenixin-20 is one of the newly identified neuropeptides with pleiotropic effects in the regulation of reproduction and other biological functions. G-protein receptor-coupled 173 (GPR173) is the putative receptor of Phoenixin-20. In the present study, we show that endothelial GPR173 is repressed upon ox-LDL stimulation in human aortic endothelial cells (HAECs). We further elaborate on the hypothesis that GPR173 could be involved in the pathogenesis of atherosclerosis through a series of experiments. Our results indicate that ox-LDL remarkably triggers the increase of ROS, NOX-4, pro-inflammatory cytokines IL-1β, IL-8, and MCP-1 expression, as well as adhesion molecules ICAM-1 and VCAM-1 release. However, the agonism of GPR173 using Phoenixin-20 significantly ameliorates all of these harmful effects from ox-LDL by suppressing the NF-κB pathway. Furthermore, we show that agonism of GPR173 by Phoenixin-20 prevents the attachment of monocytes THP-1 to endothelial cells, which is an important therapeutic approach to preventing atherogenesis. In conclusion, our study demonstrates that GPR173 agonism by Phoenixin-20 plays a protective role against ox-LDL-induced endothelial dysfunction, implying that Phoenixin-20 may have therapeutic implications in atherosclerosis.