18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload-induced maladaptive cardiac remodeling.
18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload-induced maladaptive cardiac remodeling.
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DOI：
10.1084/jem.20132011
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发表时间：
2014-07-28
期刊：
影响因子：
--
通讯作者：
Arita M
中科院分区：
文献类型：
--
作者：
Endo J;Sano M;Isobe Y;Fukuda K;Kang JX;Arai H;Arita M
巨噬细胞衍生的 18-HEPE 通过防止心脏成纤维细胞的促炎激活和随后的纤维化来保护小鼠免受心脏重塑。 N-3 多不饱和脂肪酸 (PUFA) 具有潜在的心血管益处，但其背后的机制仍知之甚少。表达秀丽隐杆线虫 n-3 脂肪酸去饱和酶的 Fat-1 转基因小鼠能够从 n-6 PUFA 产生 n-3 PUFA，表现出对压力超负荷引起的炎症和纤维化的抵抗力，以及心脏功能的降低。脂质组学分析揭示了 fat-1 转基因骨髓 (BM) 细胞中二十碳五烯酸 (EPA) 的选择性富集以及 fat-1 转基因巨噬细胞中 EPA 代谢物 18-羟基二十碳五烯酸 (18-HEPE) 的选择性富集。 BM移植实验表明，fat-1转基因BM细胞（而非fat-1转基因心脏细胞）有助于抗重塑作用，并且fat-1转基因心脏中富含18-HEPE的环境是由BM衍生细胞（最有可能是巨噬细胞）产生的。 18-HEPE 抑制培养物中巨噬细胞介导的心脏成纤维细胞的促炎性激活，并且体内施用 18-HEPE 再现了 fat-1 小鼠表型，包括对压力超负荷诱导的适应不良心脏重塑的抵抗力。
Macrophage-derived 18-HEPE protects mice from cardiac remodeling by preventing proinflammatory activation of cardiac fibroblasts and subsequent fibrosis. 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.
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DOI：
10.1084/jem.20082596
发表时间：
2009-07-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kayama Y;Minamino T;Toko H;Sakamoto M;Shimizu I;Takahashi H;Okada S;Tateno K;Moriya J;Yokoyama M;Nojima A;Yoshimura M;Egashira K;Aburatani H;Komuro I
通讯作者：
Komuro I
DOI：
10.1161/hypertensionaha.109.148635
发表时间：
2010-08
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Meléndez GC;McLarty JL;Levick SP;Du Y;Janicki JS;Brower GL
通讯作者：
Brower GL
影响因子：
24
作者：
Nodari, Savina;Triggiani, Marco;Cas, Livio Dei
通讯作者：
Cas, Livio Dei
影响因子：
5.4
作者：
Kai, Hisashi;Mori, Takahiro;Imaizumi, Tsutomu
通讯作者：
Imaizumi, Tsutomu
影响因子：
10.8
作者：
Duda, Monika K.;O'Shea, Karen M.;Stanley, William C.
通讯作者：
Stanley, William C.