ArticleJournal of lipid research2015
EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4.
Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- The Optimal Dosage and Duration of ω-3 PUFA Supplementation in Heart Failure Management: Evidence from a Network Meta-Analysis.Advances in nutrition (Bethesda, Md.) · 2025Pooled it
- Vitamin D, Marine n-3 Fatty Acids, and Primary Prevention of Cardiovascular Disease Current Evidence.Circulation research · 2020Trial
- Fatty Acids and Their Roles in Cardiac Physiology and Pathology: Mechanistic and Interventional Studies.Nutrients · 2026Review
- Maternal dietary DHA and EPA supplementation ameliorates adverse cardiac outcomes in THC-exposed rat offspring.Scientific reports · 2025Article
- Article
- Article
- New Therapeutics for Heart Failure: Focusing on cGMP Signaling.International journal of molecular sciences · 2023Review
- Marine omega-3 fatty acid supplementation and prevention of cardiovascular disease: update on the randomized trial evidence.Cardiovascular research · 2023Review
- Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events.Frontiers in cardiovascular medicine · 2023Article
- Signaling through Free Fatty Acid Receptor 4 Attenuates Cardiometabolic Disease.Physiology (Bethesda, Md.) · 2022Review
- Comment on "Activation of the Omega-3 Fatty Acid Receptor GPR120 Protects against Focal Cerebral Ischemic Injury by Preventing Inflammation and Apoptosis in Mice".Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Free fatty acid receptor 4 responds to endogenous fatty acids to protect the heart from pressure overload.Cardiovascular research · 2022Article
- Review
- Omega-3 Polyunsaturated Fatty Acids-Vascular and Cardiac Effects on the Cellular and Molecular Level (Narrative Review).International journal of molecular sciences · 2022Review
- Long-chain omega-3 polyunsaturated fatty acids and the risk of heart failure.Therapeutic advances in chronic disease · 2022Article
- Clinical significance of polyunsaturated fatty acids in the prevention of cardiovascular diseases.Frontiers in nutrition · 2022Review
- Epoxylipids and soluble epoxide hydrolase in heart diseases.Biochemical pharmacology · 2022Review
- FFAR4: A New Player in Cardiometabolic Disease?Endocrinology · 2021Review
- Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure.International journal of molecular sciences · 2021Review
- The Effects of Fish Oil on Cardiovascular Diseases: Systematical Evaluation and Recent Advance.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but standard HF therapies are ineffective. Diastolic dysfunction, often secondary to interstitial fibrosis, is common in HFpEF. Previously, we found that supra-physiologic levels of ω3-PUFAs produced by 12 weeks of ω3-dietary supplementation prevented fibrosis and contractile dysfunction following pressure overload [transverse aortic constriction (TAC)], a model that resembles aspects of remodeling in HFpEF. This raised several questions regarding ω3-concentration-dependent cardioprotection, the specific role of EPA and DHA, and the relationship between prevention of fibrosis and contractile dysfunction. To achieve more clinically relevant ω3-levels and test individual ω3-PUFAs, we shortened the ω3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ω3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ω3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ω3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ω3-PUFAs, was sufficient and required to block transforming growth factor β1-fibrotic signaling in cultured cardiac fibroblasts, suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of fibrosis could represent a novel therapy for HFpEF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.