{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:58:23Z","timestamp":1792803503666,"version":"4.5.0"},"reference-count":120,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Far Eastern Memorial Hospital Research Program","award":["FEMH 2023-C-073"],"award-info":[{"award-number":["FEMH 2023-C-073"]}],"id":[{"id":"https:\/\/ror.org\/019tq3436","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Excessive intake of free fatty acids (FFAs), especially saturated fatty acids, can lead to atherosclerosis and increase the incidence of cardiovascular diseases. FFAs also contribute to obesity, hyperlipidemia, and nonalcoholic fatty liver disease. Palmitic acid (PA) is human plasma\u2019s most abundant saturated fatty acid. It is often used to study the toxicity caused by free fatty acids in different organs, including vascular lipotoxicity. Fatty acid overload induces endothelial dysfunction through various molecular mechanisms. Endothelial dysfunction alters vascular homeostasis by reducing vasodilation and increasing proinflammatory and prothrombotic states. It is also linked to atherosclerosis, which leads to coronary artery disease, peripheral artery disease, and stroke. In this review, we summarize the latest studies, revealing the molecular mechanism of free fatty acid-induced vascular dysfunction, targeting insulin resistance, reactive oxygen species, inflammation, programmed cell death, ER stress, and mitochondrial dysfunction. Meanwhile, this review provides new strategies and perspectives for preventing and reducing the impact of cardiovascular diseases on human health through the relevant targeting molecular mechanism.<\/jats:p>","DOI":"10.3390\/antiox13121486","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T06:24:44Z","timestamp":1733379884000},"page":"1486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Targeting Insulin Resistance, Reactive Oxygen Species, Inflammation, Programmed Cell Death, ER Stress, and Mitochondrial Dysfunction for the Therapeutic Prevention of Free Fatty Acid-Induced Vascular Endothelial Lipotoxicity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-9857","authenticated-orcid":false,"given":"Chong-Sun","family":"Khoi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City 220216, Taiwan"},{"name":"Graduate School of Biotechnology and Bioengineering, College of Engineering, Yuan Ze University, Taoyuan City 320315, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City 220216, Taiwan"},{"name":"Department of Mechanical Engineering, College of Engineering, Yuan Ze University, Taoyuan City 320315, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9021-4616","authenticated-orcid":false,"given":"Chih-Kang","family":"Chiang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei City 10617, Taiwan"},{"name":"Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City 10617, Taiwan"},{"name":"Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei City 100229, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1152\/physrev.00041.2018","article-title":"Free Fatty Acid Receptors in Health and Disease","volume":"100","author":"Kimura","year":"2020","journal-title":"Physiol. 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