{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:02:26Z","timestamp":1792512146461,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2020,3,28]],"date-time":"2020-03-28T00:00:00Z","timestamp":1585353600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Endocrinology"],"published-print":{"date-parts":[[2020,3,28]]},"abstract":"<jats:p><jats:italic>\u03b2<\/jats:italic>-Endorphin, an endogenous opioid peptide, and its<jats:italic>\u03bc<\/jats:italic>-opioid receptor are expressed in brain, liver, and peripheral tissues.<jats:italic>\u03b2<\/jats:italic>-Endorphin induces endothelial dysfunction and is related to insulin resistance. We clarified the effects of<jats:italic>\u03b2<\/jats:italic>-endorphin on atherosclerosis. We assessed the effects of<jats:italic>\u03b2<\/jats:italic>-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<jats:italic>\u03b2<\/jats:italic>-endorphin on aortic lesions in<jats:italic>Apoe<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice in vivo. The<jats:italic>\u03bc<\/jats:italic>-opioid receptor (OPRM1) was expressed in THP-1 monocytes, macrophages, HASMCs, HUVECs, and human aortic endothelial cells.<jats:italic>\u03b2<\/jats:italic>-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-<jats:italic>\u03ba<\/jats:italic>B (NF-<jats:italic>\u03ba<\/jats:italic>B) and p38 phosphorylation in HUVECs.<jats:italic>\u03b2<\/jats:italic>-Endorphin significantly increased HUVEC proliferation and enhanced oxidized low-density lipoprotein-induced foam cell formation in macrophages.<jats:italic>\u03b2<\/jats:italic>-Endorphin also significantly shifted the macrophage phenotype to proinflammatory M1 rather than anti-inflammatory M2 via NF-<jats:italic>\u03ba<\/jats:italic>B phosphorylation during monocyte-macrophage differentiation and increased migration and apoptosis in association with c-jun-N-terminal kinase, p38, and NF-<jats:italic>\u03ba<\/jats:italic>B phosphorylation in HASMCs. Chronic<jats:italic>\u03b2<\/jats:italic>-endorphin infusion into<jats:italic>Apoe<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>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<jats:italic>\u03b2<\/jats:italic>-endorphin contributes to the acceleration of the progression and instability of atheromatous plaques. Thus,<jats:italic>\u03bc<\/jats:italic>-opioid receptor antagonists may be useful for the prevention and treatment of atherosclerosis.<\/jats:p>","DOI":"10.1155\/2020\/4139093","type":"journal-article","created":{"date-parts":[[2020,3,28]],"date-time":"2020-03-28T23:30:43Z","timestamp":1585438243000},"page":"1-11","source":"Crossref","is-referenced-by-count":12,"title":["<i>\u03b2<\/i>-Endorphin Mediates the Development and Instability of Atherosclerotic Plaques"],"prefix":"10.1155","volume":"2020","author":[{"given":"Taisuke","family":"Okano","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8927-6852","authenticated-orcid":true,"given":"Kengo","family":"Sato","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Medicine, Tokyo University 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