{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:51:00Z","timestamp":1787237460795,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T00:00:00Z","timestamp":1640390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-15-00361"],"award-info":[{"award-number":["19-15-00361"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hyperlipidemia manifested by high blood levels of free fatty acids (FFA) and lipoprotein triglycerides is critical for the progression of type 2 diabetes (T2D) and its cardiovascular complications via vascular endothelial dysfunction. However, attempts to assess high FFA effects in endothelial culture often result in early cell apoptosis that poorly recapitulates a much slower pace of vascular deterioration in vivo and does not provide for the longer-term studies of endothelial lipotoxicity in vitro. Here, we report that palmitate (PA), a typical FFA, does not impair, by itself, endothelial barrier and insulin signaling in human umbilical vein endothelial cells (HUVEC), but increases NO release, reactive oxygen species (ROS) generation, and protein labeling by malondialdehyde (MDA) hallmarking oxidative stress and increased lipid peroxidation. This PA-induced stress eventually resulted in the loss of cell viability coincident with loss of insulin signaling. Supplementation with 5-aminoimidazole-4-carboxamide-riboside (AICAR) increased endothelial AMP-activated protein kinase (AMPK) activity, supported insulin signaling, and prevented the PA-induced increases in NO, ROS, and MDA, thus allowing to maintain HUVEC viability and barrier, and providing the means to study the long-term effects of high FFA levels in endothelial cultures. An upgraded cell-based model reproduces FFA-induced insulin resistance by demonstrating decreased NO production by vascular endothelium.<\/jats:p>","DOI":"10.3390\/ijms23010211","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["AICAR Protects Vascular Endothelial Cells from Oxidative Injury Induced by the Long-Term Palmitate Excess"],"prefix":"10.3390","volume":"23","author":[{"given":"Mikhail V.","family":"Samsonov","sequence":"first","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita V.","family":"Podkuychenko","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7889-3337","authenticated-orcid":false,"given":"Asker Y.","family":"Khapchaev","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene E.","family":"Efremov","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Yanushevskaya","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana N.","family":"Vlasik","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim Z.","family":"Lankin","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iurii S.","family":"Stafeev","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim V.","family":"Skulachev","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina V.","family":"Shestakova","sequence":"additional","affiliation":[{"name":"Diabetes Institute, Endocrinology Research Center, 117036 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1460-971X","authenticated-orcid":false,"given":"Alexander V.","family":"Vorotnikov","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir P.","family":"Shirinsky","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1017\/S0029665118002598","article-title":"Turning over our fat stores: The key to metabolic health Blaxter Award Lecture 2018","volume":"78","author":"Frayn","year":"2019","journal-title":"Proc. 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