{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:17:52Z","timestamp":1793085472893,"version":"4.5.0"},"reference-count":186,"publisher":"Oxford University Press (OUP)","issue":"Supplement_J","license":[{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Heart Lung Blood Institutes","award":["R01 HL130099"],"award-info":[{"award-number":["R01 HL130099"]}]},{"name":"National Heart Lung Blood Institutes","award":["R01 HL152215"],"award-info":[{"award-number":["R01 HL152215"]}]},{"name":"National Heart Lung Blood Institutes","award":["K01 HL133416"],"award-info":[{"award-number":["K01 HL133416"]}]},{"name":"Amarin Pharma, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with well-controlled low-density lipoprotein cholesterol levels, but persistent high triglycerides, remain at increased risk for cardiovascular events as evidenced by multiple genetic and epidemiologic studies, as well as recent clinical outcome trials. While many trials of low-dose \u03c93-polyunsaturated fatty acids (\u03c93-PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have shown mixed results to reduce cardiovascular events, recent trials with high-dose \u03c93-PUFAs have reignited interest in \u03c93-PUFAs, particularly EPA, in cardiovascular disease (CVD). REDUCE-IT demonstrated that high-dose EPA (4\u2009g\/day icosapent-ethyl) reduced a composite of clinical events by 25% in statin-treated patients with established CVD or diabetes and other cardiovascular risk factors. Outcome trials in similar statin-treated patients using DHA-containing high-dose \u03c93 formulations have not yet shown the benefits of EPA alone. However, there are data to show that high-dose \u03c93-PUFAs in patients with acute myocardial infarction had reduced left ventricular remodelling, non-infarct myocardial fibrosis, and systemic inflammation. \u03c93-polyunsaturated fatty acids, along with their metabolites, such as oxylipins and other lipid mediators, have complex effects on the cardiovascular system. Together they target free fatty acid receptors and peroxisome proliferator-activated receptors in various tissues to modulate inflammation and lipid metabolism. Here, we review these multifactorial mechanisms of \u03c93-PUFAs in view of recent clinical findings. These findings indicate physico-chemical and biological diversity among \u03c93-PUFAs that influence tissue distributions as well as disparate effects on membrane organization, rates of lipid oxidation, as well as various receptor-mediated signal transduction pathways and effects on gene expression.<\/jats:p>","DOI":"10.1093\/eurheartj\/suaa115","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T16:44:39Z","timestamp":1602002679000},"page":"J3-J20","source":"Crossref","is-referenced-by-count":41,"title":["Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites"],"prefix":"10.1093","volume":"22","author":[{"given":"Timothy D","family":"O\u2019Connell","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota, 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard Preston","family":"Mason","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Budoff","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann Marie","family":"Navar","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Duke Clinical Research Institute, Duke University, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory C","family":"Shearer","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The Pennsylvania State University, 110 Chandlee Laboratory, University Park, PA 16802, 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