EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure

Potential role of free fatty acid receptor 4

Julie A. Eclov, Qingwen Qian, Rebecca Redetzke, Quanhai Chen, Steven C. Wu, Chastity L. Healy, Steven B. Ortmeier, Erin Harmon, Gregory C. Shearer, Timothy D. O'Connell

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 EPAand 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 proteincoupled 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.

Original languageEnglish (US)
Pages (from-to)2297-2308
Number of pages12
JournalJournal of Lipid Research
Volume56
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Nonesterified Fatty Acids
Fibrosis
Nutrition
Heart Failure
Pressure
Constriction
Fibroblasts
Diet
Transforming Growth Factors
Dietary Supplements
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Eclov, J. A., Qian, Q., Redetzke, R., Chen, Q., Wu, S. C., Healy, C. L., ... O'Connell, T. D. (2015). EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: Potential role of free fatty acid receptor 4. Journal of Lipid Research, 56(12), 2297-2308. https://doi.org/10.1194/jlr.M062034
Eclov, Julie A. ; Qian, Qingwen ; Redetzke, Rebecca ; Chen, Quanhai ; Wu, Steven C. ; Healy, Chastity L. ; Ortmeier, Steven B. ; Harmon, Erin ; Shearer, Gregory C. ; O'Connell, Timothy D. / EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure : Potential role of free fatty acid receptor 4. In: Journal of Lipid Research. 2015 ; Vol. 56, No. 12. pp. 2297-2308.
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Eclov, JA, Qian, Q, Redetzke, R, Chen, Q, Wu, SC, Healy, CL, Ortmeier, SB, Harmon, E, Shearer, GC & O'Connell, TD 2015, 'EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: Potential role of free fatty acid receptor 4', Journal of Lipid Research, vol. 56, no. 12, pp. 2297-2308. https://doi.org/10.1194/jlr.M062034

EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure : Potential role of free fatty acid receptor 4. / Eclov, Julie A.; Qian, Qingwen; Redetzke, Rebecca; Chen, Quanhai; Wu, Steven C.; Healy, Chastity L.; Ortmeier, Steven B.; Harmon, Erin; Shearer, Gregory C.; O'Connell, Timothy D.

In: Journal of Lipid Research, Vol. 56, No. 12, 01.12.2015, p. 2297-2308.

Research output: Contribution to journalArticle

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T1 - EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure

T2 - Potential role of free fatty acid receptor 4

AU - Eclov, Julie A.

AU - Qian, Qingwen

AU - Redetzke, Rebecca

AU - Chen, Quanhai

AU - Wu, Steven C.

AU - Healy, Chastity L.

AU - Ortmeier, Steven B.

AU - Harmon, Erin

AU - Shearer, Gregory C.

AU - O'Connell, Timothy D.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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 EPAand 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 proteincoupled 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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