A Metabolic Basis for Endothelial-to-Mesenchymal Transition.
A Metabolic Basis for Endothelial-to-Mesenchymal Transition.
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DOI：
10.1016/j.molcel.2018.01.010
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发表时间：
2018-02-15
期刊：
影响因子：
16
通讯作者：
Finkel T
中科院分区：
文献类型：
--
作者：
Xiong J;Kawagishi H;Yan Y;Liu J;Wells QS;Edmunds LR;Fergusson MM;Yu ZX;Rovira II;Brittain EL;Wolfgang MJ;Jurczak MJ;Fessel JP;Finkel T
内皮细胞向间质细胞转化（EndoMT）是一个细胞过程，通常由生长因子β（TGFβ）家族的配体启动。尽管正常心脏瓣膜发育需要，但失调的EndoMT与广泛的病理状况有关。在这里，我们证明，内皮脂肪酸氧化（FAO）是一个关键的在体外和体内调节EndoMT。我们进一步表明，这种粮农组织依赖的代谢调节EndoMT发生通过改变乙酰辅酶A水平。通过内皮肉毒碱棕榈酰转移酶II（Cpt 2 E-KO）的条件性缺失破坏FAO增加胚胎EndoMT的大小，导致心脏瓣膜肥大。与EndoMT的已知病理学效应一致，成年Cpt 2 E-KO小鼠在多个血管床中表现出增加的渗透性。总之，这些结果表明，内皮FAO是维持内皮细胞命运所必需的，并且内皮代谢的治疗性操纵可以为治疗越来越多的EndoMT相关病理状况提供基础。Xiong等人证明，内皮脂肪酸氧化（FAO）是内皮-间充质转化（EndoMT）的关键体外和体内调节剂，并且内皮代谢的治疗操作可以为治疗越来越多的EndoMT相关病理状况提供基础。
Endothelial-to-mesenchymal-transition (EndoMT) is a cellular process often initiated by the growth factor β (TGFβ) family of ligands. Although required for normal heart valve development, deregulated EndoMT is linked to a wide range of pathological conditions. Here, we demonstrate that endothelial fatty acid oxidation (FAO) is a critical in vitro and in vivo regulator of EndoMT. We further show that this FAO-dependent metabolic regulation of EndoMT occurs through alterations in acetyl-CoA levels. Disruption of FAO via conditional deletion of endothelial carnitine palmitoyltransferase II (Cpt2E-KO) augments the magnitude of embryonic EndoMT, resulting in thicken cardiac valves. Consistent with the known pathological effects of EndoMT, adult Cpt2E-KO mice demonstrate increased permeability in multiple vascular beds. Taken together, these results demonstrate that endothelial FAO is required to maintain endothelial cell fate and that therapeutic manipulation of endothelial metabolism could provide the basis for treating a growing number of EndoMT-linked pathological conditions. Xiong et al. demonstrate that endothelial fatty acid oxidation (FAO) is a critical in vitro and in vivo regulator of endothelial-to-mesenchymal-transition (EndoMT) and that therapeutic manipulation of endothelial metabolism could provide the basis for treating a growing number of EndoMT-linked pathological conditions.
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影响因子：
29
作者：
Lee JV;Carrer A;Shah S;Snyder NW;Wei S;Venneti S;Worth AJ;Yuan ZF;Lim HW;Liu S;Jackson E;Aiello NM;Haas NB;Rebbeck TR;Judkins A;Won KJ;Chodosh LA;Garcia BA;Stanger BZ;Feldman MD;Blair IA;Wellen KE
通讯作者：
Wellen KE
影响因子：
2.5
作者：
Alva, JA;Zovein, AC;Iruela-Arispe, ML
通讯作者：
Iruela-Arispe, ML
影响因子：
64.5
作者：
De Bock, Katrien;Georgiadou, Maria;Carmeliet, Peter
通讯作者：
Carmeliet, Peter
DOI：
10.1007/978-3-319-51436-9_13
发表时间：
2017-01-01
期刊：
KIDNEY DEVELOPMENT AND DISEASE
影响因子：
--
作者：
Cruz-Solbes, Ana S.;Youker, Keith
通讯作者：
Youker, Keith
影响因子：
15.9
作者：
Magrini, Elena;Villa, Alessandra;Cavallaro, Ugo
通讯作者：
Cavallaro, Ugo