TMAO Upregulates Members of the miR-17/92 Cluster and Impacts Targets Associated with Atherosclerosis.
TMAO Upregulates Members of the miR-17/92 Cluster and Impacts Targets Associated with Atherosclerosis.
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TMAO上调miR-17/92簇的成员，并影响与动脉粥样硬化有关的靶标。
DOI：
10.3390/ijms232012107
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发表时间：
2022-10-11
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
动脉粥样硬化是心血管疾病的一个标志，生活方式对其发病和进展有很大影响。营养素已被证明可调节miR - 17/92簇，其在血管内皮功能和动脉粥样硬化中起作用。在动物食品中发现的胆碱、甜菜碱和左旋肉碱被肠道微生物群代谢为三甲胺（TMA）。然后TMA被氧化为氧化三甲胺（TMAO），它与动脉粥样硬化有关。我们的目的是研究TMAO是否调节miR - 17/92簇的表达，以及这种调节对与动脉粥样硬化和炎症相关的靶基因表达的影响。我们在不同时间点用6μM的TMAO处理HepG - 2细胞、THP - 1细胞、小鼠肝脏类器官和人外周血单个核细胞。TMAO增加了该簇所有被分析成员的表达，但在小鼠肝脏类器官和原代人巨噬细胞中的miR - 20a - 5p除外。SERPINE1和IL - 12A的基因和蛋白质水平升高。两者都与动脉粥样硬化和心血管疾病（CVD）有关，并且受miR - 17 - 92簇间接调节。我们得出结论，TMAO调节miR - 17/92簇的表达，这种调节可通过IL - 12A促进炎症，通过SERPINE1表达促进血液凝固，最终可能促进动脉粥样硬化和心血管疾病。
Atherosclerosis is a hallmark of cardiovascular disease, and lifestyle strongly impacts its onset and progression. Nutrients have been shown to regulate the miR-17/92 cluster, with a role in endothelial function and atherosclerosis. Choline, betaine, and L-carnitine, found in animal foods, are metabolized into trimethylamine (TMA) by the gut microbiota. TMA is then oxidized to TMAO, which has been associated with atherosclerosis. Our aim was to investigate whether TMAO modulates the expression of the miR-17/92 cluster, along with the impact of this modulation on the expression of target genes related to atherosclerosis and inflammation. We treated HepG-2 cells, THP-1 cells, murine liver organoids, and human peripheral mononuclear cells with 6 µM of TMAO at different timepoints. TMAO increased the expression of all analyzed members of the cluster, except for miR-20a-5p in murine liver organoids and primary human macrophages. Genes and protein levels of SERPINE1 and IL-12A increased. Both have been associated with atherosclerosis and cardiovascular disease (CDVD) and are indirectly modulated by the miR-17-92 cluster. We concluded that TMAO modulates the expression of the miR-17/92 cluster and that such modulation could promote inflammation through IL-12A and blood clotting through SERPINE1 expression, which could ultimately promote atherosclerosis and CVD.
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影响因子：
4.8
作者：
Danielson, Laura S.;Park, David S.;Hernando, Eva
通讯作者：
Hernando, Eva
影响因子：
8.8
作者：
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影响因子：
2.7
作者：
Huang, Y.;Tang, S.;Feng, Y-q
通讯作者：
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影响因子：
4.8
作者：
Andraos S;Jones B;Lange K;Clifford SA;Thorstensen EB;Kerr JA;Wake M;Saffery R;Burgner DP;O'Sullivan JM
通讯作者：
O'Sullivan JM
影响因子：
5.2
作者：
Daimiel L;Micó V;Valls RM;Pedret A;Motilva MJ;Rubió L;Fitó M;Farrás M;Covas MI;Solá R;Ordovás JM
通讯作者：
Ordovás JM