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


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 ?3-PUFAs produced by 12 weeks of ?3-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 ?3-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 ?3-levels and test individual ?3-PUFAs, we shortened the ?3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ?3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ?3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ?3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ?3-PUFAs, was sufficient and required to block transforming growth factor ?1-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.

SUBMITTER: Eclov JA 

PROVIDER: S-EPMC4655986 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Eclov Julie A JA   Qian Qingwen Q   Redetzke Rebecca R   Chen Quanhai Q   Wu Steven C SC   Healy Chastity L CL   Ortmeier Steven B SB   Harmon Erin E   Shearer Gregory C GC   O'Connell Timothy D TD  

Journal of lipid research 20151004 12


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 se  ...[more]

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