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

doi:10.1194/jlr.M062034

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EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

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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 and Timothy D. O'Connell

Journal of lipid research, Vol.56(12), pp.2297-2308

12/2015

DOI: 10.1194/jlr.M062034

PMCID: PMC4655986

PMID: 26435012

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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.

docosahexaenoic acid

eicosapentaenoic acid

fibroblast

omega-3 polyunsaturated fatty acids

transverse aortic constriction

Details

Title: Subtitle: EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4
Creators: Julie A. Eclov - University of Minnesota
Qingwen Qian - Sanford Research
Rebecca Redetzke - Pennsylvania State University
Quanhai Chen - Sanford Research
Steven C. Wu - University of Minnesota
Chastity L. Healy - University of Minnesota
Steven B. Ortmeier - Sanford Research
Erin Harmon - Sanford Research
Gregory C. Shearer - Pennsylvania State University
Timothy D. O'Connell - University of Minnesota
Resource Type: Journal article
Publication Details: Journal of lipid research, Vol.56(12), pp.2297-2308
DOI: 10.1194/jlr.M062034
PMID: 26435012
PMCID: PMC4655986
NLM abbreviation: J Lipid Res
ISSN: 0022-2275
eISSN: 1539-7262
Publisher: Elsevier Inc
Language: English
Date published: 12/2015
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984420845802771

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