18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload-induced maladaptive cardiac remodeling

Jin Endo, Motoaki Sano, Yosuke Isobe, Keiichi Fukuda, Jing X. Kang, Hiroyuki Arai, Makoto Arita

Research output: Contribution to journalArticle

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Abstract

N-3 polyunsaturated fatty acids (PUFAs) have potential cardiovascular benefit, although the mechanisms underlying this effect remain poorly understood. Fat-1 transgenic mice expressing Caenorhabditis elegans n-3 fatty acid desaturase, which is capable of producing n-3 PUFAs from n-6 PUFAs, exhibited resistance to pressure overload-induced inflammation and fibrosis, as well as reduced cardiac function. Lipidomic analysis revealed selective enrichment of eicosapentaenoic acid (EPA) in fat-1 transgenic bone marrow (BM) cells and EPA-metabolite 18-hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 transgenic macrophages. BM transplantation experiments revealed that fat-1 transgenic BM cells, but not fat-1 transgenic cardiac cells, contributed to the antiremodeling effect and that the 18- HEPE-rich milieu in the fat-1 transgenic heart was generated by BM-derived cells, most likely macrophages. 18-HEPE inhibited macrophage-mediated proinflammatory activation of cardiac fibroblasts in culture, and in vivo administration of 18-HEPE reproduced the fat-1 mice phenotype, including resistance to pressure overload-induced maladaptive cardiac remodeling.

Original languageEnglish
Pages (from-to)1673-1687
Number of pages15
JournalJournal of Experimental Medicine
Volume211
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Omega-3 Fatty Acids
Fats
Macrophages
Pressure
Acids
Bone Marrow Cells
Eicosapentaenoic Acid
Fatty Acid Desaturases
Caenorhabditis elegans
Bone Marrow Transplantation
Unsaturated Fatty Acids
Transgenic Mice
Fibrosis
Fibroblasts
Inflammation
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload-induced maladaptive cardiac remodeling. / Endo, Jin; Sano, Motoaki; Isobe, Yosuke; Fukuda, Keiichi; Kang, Jing X.; Arai, Hiroyuki; Arita, Makoto.

In: Journal of Experimental Medicine, Vol. 211, No. 8, 2014, p. 1673-1687.

Research output: Contribution to journalArticle

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AU - Kang, Jing X.

AU - Arai, Hiroyuki

AU - Arita, Makoto

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