| First Author | Endo J | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 8 | Pages | 1673-87 |
| PubMed ID | 25049337 | Mgi Jnum | J:214720 |
| Mgi Id | MGI:5603933 | Doi | 10.1084/jem.20132011 |
| Citation | Endo J, et al. (2014) 18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload-induced maladaptive cardiac remodeling. J Exp Med 211(8):1673-87 |
| abstractText | 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. |
