The DOI matches its Crossref record; 74 of the 76 references it cites were found in a registry or an index.
Eicosapentaenoic acid reduces membrane fluidity, inhibits cholesterol domain formation, and normalizes bilayer width in atherosclerotic-like model membranes
Open accessAbstract
Cholesterol crystalline domains characterize atherosclerotic membranes, altering vascular signaling and function. Omega-3 fatty acids reduce membrane lipid peroxidation and subsequent cholesterol domain formation. We evaluated non-peroxidation-mediated effects of eicosapentaenoic acid (EPA), other TG-lowering agents, docosahexaenoic acid (DHA), and other long-chain fatty acids on membrane fluidity, bilayer width, and cholesterol domain formation in model membranes. In membranes prepared at 1.5:1 cholesterol-to-phospholipid (C/P) mole ratio (creating pre-existing domains), EPA, glycyrrhizin, arachidonic acid, and alpha linolenic acid promoted the greatest reductions in cholesterol domains (by 65.5%, 54.9%, 46.8%, and 45.2%, respectively) compared to controls; other treatments had modest effects. EPA effects on cholesterol domain formation were dose-dependent. In membranes with 1:1 C/P (predisposing domain formation), DHA, but not EPA, dose-dependently increased membrane fluidity. DHA also induced cholesterol domain formation without affecting temperature-induced changes in-bilayer unit cell periodicity relative to controls (d-space; 57Å-55Å over 15-30°C). Together, these data suggest simultaneous formation of distinct cholesterol-rich ordered domains and cholesterol-poor disordered domains in the presence of DHA. By contrast, EPA had no effect on cholesterol domain formation and produced larger d-space values relative to controls (60Å-57Å; p<0.05) over the same temperature range, suggesting a more uniform maintenance of lipid dynamics despite the presence of cholesterol. These data indicate that EPA and DHA had different effects on membrane bilayer width, membrane fluidity, and cholesterol crystalline domain formation; suggesting omega-3 fatty acids with differing chain length or unsaturation may differentially influence membrane lipid dynamics and structural organization as a result of distinct phospholipid/sterol interactions.
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“a broad literature examining effects of EPA vs EPA/DHA at the molecular and cellular levels,39, 40, 41, 42 their effects at the level of atherosclerotic plaque quantifiable with clinical imaging,8 and their effects at the clinical endpoint level evidenced in the RCT literature reviewed here, all suggest more robust benefit with purified EPA rather than mixed EPA/DHA.”
From Effects of Eicosapentaenoic Acid vs Eicosapentaenoic/Docosahexaenoic Acids on Cardiovascular Mortality (2025) · cites this paper as [42]
In the citing paper
“Multiple epidemiological and genetic analyses have demonstrated an independent association with increased cardiovascular risk (14)”
From Effects of Icosapent Ethyl on Total Ischemic Events (2019) · cites this paper as [18]
In the citing paper
“EPA and DHA interact differently with cellular membranes”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [27]
In the citing paper
“prevents lipid oxidation”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [27]
In the citing paper
“compared with DHA, EPA has a more stable, extended structure”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [27]
In the citing paper
“promotes membrane stability”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [27]
In the citing paper
“inhibits inflammation”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [27]
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Citations
Cites
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Remnant Cholesterol as a Causal Risk Factor for Ischemic Heart Disease
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n–3 Fatty Acids and Cardiovascular Events after Myocardial Infarction
Kromhout, D., Giltay, E. J., & Geleijnse, J. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003603 · Cited by 936
n–3 Fatty Acids and Cardiovascular Outcomes in Patients with Dysglycemia
The ORIGIN Trial Investigators (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1203859 · Cited by 929
Flagged first, then by citations
2 of the 76 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Small, 1988, Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry, Arterioscler. Thromb. Vasc. Biol., 8, 103
- Niki, 2012, Effects of additional eicosapentaenoic adic to statin therapy on inflammatory cytokines and the tissue characterization of coronary plaque assessed by integrated backscatter intravascular ultrasound systems [abstract 14434], Circulation, 126, 14434
Cited by
Sorted by citations
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., Granowitz, C., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812792 · Cited by 3,317
Emerging Mechanisms of Cardiovascular Protection for the Omega-3 Fatty Acid Eicosapentaenoic Acid
Mason, R. P., Libby, P., & Bhatt, D. L. (2020) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.119.313286 · Cited by 407
Self-citationBailly, C., & Vergoten, G. (2020) · Pharmacology and Therapeutics · doi:10.1016/j.pharmthera.2020.107618 · Cited by 261
Dietary fatty acids fine-tune Piezo1 mechanical response
Romero, L. O., Massey, A. E., Mata‐Daboin, A., Sierra-Valdez, F. J., Chauhan, S. C., Cordero-Morales, J. F., & Vásquez, V. (2019) · Nature Communications · doi:10.1038/s41467-019-09055-7 · Cited by 266
Effects of Icosapent Ethyl on Total Ischemic Events
Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., Granowitz, C., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.02.032 · Cited by 259
Metadata
- Authors
- Mason, R. P., Jacob, R. F., Shrivastava, S., Sherratt, S. C. R., & Chattopadhyay, A.
- Affiliations
- Brigham and Women's Hospital (US)
- Centre for Cellular and Molecular Biology (IN)
- Corresponding author
- Mason, R. Preston
- Venue
- Biochimica et Biophysica Acta (BBA) - Biomembranes
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 1858
- Issue
- 12
- Pages
- 3131-3140
- ISSN
- 0005-2736 (ISSN-L)
- OpenAlex
- W2527894800
- Cited by
- 179
- References
- 76
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 25 · 2023: 22 · 2022: 26 · 2021: 27 · 2020: 23 · 2019: 17 · 2018: 8 · 2017: 8
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Biomembranes (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Amarin Pharma
- Bangladesh Council of Scientific and Industrial Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- eicosapentaenoic acid, docosahexaenoic acid, omega-3 fatty acids, membrane fluidity, atherosclerosis, model membranes, cholesterol/phospholipid ratio, lipid peroxidation, long-chain fatty acids, glycyrrhizin, arachidonic acid, alpha-linolenic acid, lipid dynamics
- MeSH terms
- Cholesterol, Docosahexaenoic Acids, Dose-Response Relationship, Drug, Humans, Lipid Bilayers, Membrane Fluidity, Eicosapentaenoic Acid, Atherosclerosis
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