{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:55:39Z","timestamp":1791262539527,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,6]],"date-time":"2020-06-06T00:00:00Z","timestamp":1591401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2015R1A5A2009124"],"award-info":[{"award-number":["2015R1A5A2009124"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A2B6004664"],"award-info":[{"award-number":["2018R1A2B6004664"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction than glucose itself. Recent reports showed that high glucose and MGO induced endoplasmic reticulum (ER) stress and myocyte apoptosis in ischemic heart disease was inhibited by apelin. The goal of the study is to investigate the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress in endothelial cells, and to examine whether apelin-13, a cytoprotective polypeptide ligand, protects MGO-induced aortic endothelial dysfunction. MGO-induced ER stress and apoptosis were determined by immunoblotting and MTT assay in HUVECs. Aortic endothelial dysfunction was addressed by en face immunostaining and acetylcholine-induced vasodilation analysis with aortic rings from mice treated with MGO in the presence or absence of apelin ex vivo. TUDCA, an inhibitor of ER stress, inhibited MGO-induced apoptosis and reduction of cell viability, suggesting that MGO signaling to endothelial apoptosis is mediated via ER stress, which leads to activation of unfolded protein responses (UPR). In addition, MGO-induced UPR and aortic endothelial dysfunction were significantly diminished by apelin-13. Finally, this study showed that apelin-13 protects MGO-induced UPR and endothelial apoptosis through the AMPK pathway. Apelin-13 reduces MGO-induced UPR and endothelial dysfunction via regulating the AMPK activating pathway, suggesting the therapeutic potential of apelin-13 in diabetic cardiovascular complications.<\/jats:p>","DOI":"10.3390\/ijms21114069","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T05:16:14Z","timestamp":1591679774000},"page":"4069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Apelin-13 Inhibits Methylglyoxal-Induced Unfolded Protein Responses and Endothelial Dysfunction via Regulating AMPK Pathway"],"prefix":"10.3390","volume":"21","author":[{"given":"Sujin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Smart-Aging Convergence Research Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suji","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Smart-Aging Convergence Research Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ae-Rang","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Smart-Aging Convergence Research Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoung Chul","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Smart-Aging Convergence Research Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yun","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Hoon","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Smart-Aging Convergence Research Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1056\/NEJM199807233390404","article-title":"Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction","volume":"339","author":"Haffner","year":"1998","journal-title":"N. 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