%0 Journal Article
%T ¦Â-Endorphin Mediates the Development and Instability of Atherosclerotic Plaques
%A Hirano
%A Tsutomu
%A Koide
%A Ayaka
%A Mori
%A Yusaku
%A Okano
%A Taisuke
%A Sato
%A Kengo
%A Seki
%A Tomomi
%A Shibata
%A Koichiro
%A Shirai
%A Remina
%A Tezuka
%A Hitomi
%A Watanabe
%A Takuya
%A Yamashita
%A Tomoyuki
%J -
%D 2020
%R https://doi.org/10.1155/2020/4139093
%X ¦Â-Endorphin, an endogenous opioid peptide, and its ¦Ì-opioid receptor are expressed in brain, liver, and peripheral tissues. ¦Â-Endorphin induces endothelial dysfunction and is related to insulin resistance. We clarified the effects of ¦Â-endorphin on atherosclerosis. We assessed the effects of ¦Â-endorphin on the inflammatory response and monocyte adhesion in human umbilical vein endothelial cells (HUVECs), foam cell formation, and the inflammatory phenotype in THP-1 monocyte-derived macrophages, and migration and proliferation of human aortic smooth muscle cells (HASMCs) in vitro. We also assessed the effects of ¦Â-endorphin on aortic lesions in Apoe£¿/£¿ mice in vivo. The ¦Ì-opioid receptor (OPRM1) was expressed in THP-1 monocytes, macrophages, HASMCs, HUVECs, and human aortic endothelial cells. ¦Â-Endorphin significantly increased THP-1 monocyte adhesion to HUVECs and induced upregulation of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin via nuclear factor-¦ÊB (NF-¦ÊB) and p38 phosphorylation in HUVECs. ¦Â-Endorphin significantly increased HUVEC proliferation and enhanced oxidized low-density lipoprotein-induced foam cell formation in macrophages. ¦Â-Endorphin also significantly shifted the macrophage phenotype to proinflammatory M1 rather than anti-inflammatory M2 via NF-¦ÊB phosphorylation during monocyte-macrophage differentiation and increased migration and apoptosis in association with c-jun-N-terminal kinase, p38, and NF-¦ÊB phosphorylation in HASMCs. Chronic ¦Â-endorphin infusion into Apoe£¿/£¿ mice significantly aggravated the development of aortic atherosclerotic lesions, with an increase in vascular inflammation and the intraplaque macrophage/smooth muscle cell ratio, an index of plaque instability. Our study provides the first evidence that ¦Â-endorphin contributes to the acceleration of the progression and instability of atheromatous plaques. Thus, ¦Ì-opioid receptor antagonists may be useful for the prevention and treatment of atherosclerosis
%U https://www.hindawi.com/journals/ije/2020/4139093/