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

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.

• Authors: Jin Endo, Motoaki Sano, Yosuke Isobe, Keiichi Fukuda, Jing X Kang, Hiroyuki Arai, Makoto Arita
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 211 Issue 8 Pg. 1673-87 (Jul 28 2014) ISSN: 1540-9538 [Electronic] United States
• PMID: 25049337 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Endo et al.

Chemical References

• 18(R)-hydroxyeicosapentaenoic acid
• Cadherins
• Cardiotonic Agents
• fat1 protein, mouse
• Eicosapentaenoic Acid

Topics

• Animals
• Aorta (pathology)
• Bone Marrow Cells (pathology)
• Cadherins (metabolism)
• Cardiotonic Agents (metabolism)
• Coculture Techniques
• Constriction, Pathologic
• Eicosapentaenoic Acid (administration & dosage, analogs & derivatives, blood, pharmacology)
• Fibroblasts (drug effects, pathology)
• Fibrosis
• Gene Expression Profiling
• Humans
• Inflammation (pathology)
• Lipid Metabolism (drug effects, genetics)
• Macrophages (drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Myocardium (pathology)
• Pressure
• Ventricular Function, Left (drug effects)