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Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites

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 ω3-poly...

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Autores principales: O’Connell, Timothy D, Mason, Richard Preston, Budoff, Matthew J, Navar, Ann Marie, Shearer, Gregory C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537803/
https://www.ncbi.nlm.nih.gov/pubmed/33061864
http://dx.doi.org/10.1093/eurheartj/suaa115
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author O’Connell, Timothy D
Mason, Richard Preston
Budoff, Matthew J
Navar, Ann Marie
Shearer, Gregory C
author_facet O’Connell, Timothy D
Mason, Richard Preston
Budoff, Matthew J
Navar, Ann Marie
Shearer, Gregory C
author_sort O’Connell, Timothy D
collection PubMed
description 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 ω3-polyunsaturated fatty acids (ω3-PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have shown mixed results to reduce cardiovascular events, recent trials with high-dose ω3-PUFAs have reignited interest in ω3-PUFAs, particularly EPA, in cardiovascular disease (CVD). REDUCE-IT demonstrated that high-dose EPA (4 g/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 ω3 formulations have not yet shown the benefits of EPA alone. However, there are data to show that high-dose ω3-PUFAs in patients with acute myocardial infarction had reduced left ventricular remodelling, non-infarct myocardial fibrosis, and systemic inflammation. ω3-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 ω3-PUFAs in view of recent clinical findings. These findings indicate physico-chemical and biological diversity among ω3-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.
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spelling pubmed-75378032020-10-13 Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites O’Connell, Timothy D Mason, Richard Preston Budoff, Matthew J Navar, Ann Marie Shearer, Gregory C Eur Heart J Suppl Articles 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 ω3-polyunsaturated fatty acids (ω3-PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have shown mixed results to reduce cardiovascular events, recent trials with high-dose ω3-PUFAs have reignited interest in ω3-PUFAs, particularly EPA, in cardiovascular disease (CVD). REDUCE-IT demonstrated that high-dose EPA (4 g/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 ω3 formulations have not yet shown the benefits of EPA alone. However, there are data to show that high-dose ω3-PUFAs in patients with acute myocardial infarction had reduced left ventricular remodelling, non-infarct myocardial fibrosis, and systemic inflammation. ω3-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 ω3-PUFAs in view of recent clinical findings. These findings indicate physico-chemical and biological diversity among ω3-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. Oxford University Press 2020-10-06 /pmc/articles/PMC7537803/ /pubmed/33061864 http://dx.doi.org/10.1093/eurheartj/suaa115 Text en Published on behalf of the European Society of Cardiology. © The Author(s) 2020. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Articles
O’Connell, Timothy D
Mason, Richard Preston
Budoff, Matthew J
Navar, Ann Marie
Shearer, Gregory C
Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites
title Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites
title_full Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites
title_fullStr Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites
title_full_unstemmed Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites
title_short Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites
title_sort mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537803/
https://www.ncbi.nlm.nih.gov/pubmed/33061864
http://dx.doi.org/10.1093/eurheartj/suaa115
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