DNA Methyltransferase 3b Accelerates the Process of Atherosclerosis.

IF 1.9 4区经济学 Q2 ECONOMICS

Empirica Pub Date : 2022-04-05 eCollection Date: 2022-01-01 DOI:10.1155/2022/5249367

Ling Zhu, Lei Jia, Na Liu, Runmiao Wu, Gongchang Guan, Rutai Hui, Yujie Xing, Yong Zhang, Junkui Wang

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引用次数: 5

Abstract

Background: DNA methylation plays a key role in establishing cell type-specific gene expression profiles and patterns in atherosclerosis. The underlying mechanism remains unclear. Previous studies have shown that DNA methyltransferase 3b (DNMT3b) may play an important role in atherosclerosis. This study aimed to establish the regulatory role of DNMT3b in the development of atherosclerosis.

Methods: We constructed a viral vector carrying Dnmt3b shRNA to transduce ApoE^-/- mice. Meanwhile, healthy human peripheral blood Treg cells were treated with inhibitor of DNMT3b (AZA and EGCG) or transduced with DNMT3b shRNA.

Results: It showed that Dnmt3b silencing attenuated atherosclerosis, including decreased lesion size and macrophage content and increased collagen and smooth muscle cells content in ApoE^-/- mice. To further investigate the possible mechanisms, combined with previous studies by our group, we showed that Foxp3-TSDR methylation level was significantly reduced Foxp3 expression and peripheral blood Treg levels were significantly increased by Dnmt3b shRNA vector transduction in animals committed to western diet for 12 and 18 weeks. Consistently, inhibition of DNMT3b (AZA and EGCG) decreased the expression levels of DNMT3b, which can increase the expression levels of FOXP3, and increase the levels of TGF-β and IL-10 and decrease the levels of IL-β and IFN-γ. After transduction with DNMT3b shRNA, the effect was more obvious.

Conclusions: DNMT3b accelerated atherosclerosis, and may be associated with FOXP3 hypermethylation status in regulatory T cells.

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DNA 甲基转移酶 3b 加速动脉粥样硬化的进程

背景：DNA 甲基化在动脉粥样硬化中建立细胞类型特异性基因表达谱和模式方面起着关键作用。其潜在机制仍不清楚。先前的研究表明，DNA 甲基转移酶 3b (DNMT3b) 可能在动脉粥样硬化中发挥重要作用。本研究旨在确定 DNMT3b 在动脉粥样硬化发病过程中的调控作用：方法：我们构建了携带 Dnmt3b shRNA 的病毒载体转染载脂蛋白E-/-小鼠。方法：我们构建了携带Dnmt3b shRNA的病毒载体转染载脂蛋白E-/-小鼠，同时用DNMT3b抑制剂（AZA和EGCG）处理或用DNMT3b shRNA转染健康人外周血Treg细胞：结果表明，沉默Dnmt3b可减轻载脂蛋白E-/-小鼠的动脉粥样硬化，包括减少病变大小和巨噬细胞含量，增加胶原蛋白和平滑肌细胞含量。为了进一步探究可能的机制，结合本研究组之前的研究，我们发现在西式饮食12周和18周的动物中，通过Dnmt3b shRNA载体转导，Foxp3-TSDR甲基化水平显著降低，外周血Treg水平显著升高。同样，抑制 DNMT3b（AZA 和 EGCG）可降低 DNMT3b 的表达水平，而 DNMT3b 可增加 FOXP3 的表达水平，增加 TGF-β 和 IL-10 的水平，降低 IL-β 和 IFN-γ 的水平。用 DNMT3b shRNA 转导后，效果更为明显：结论：DNMT3b会加速动脉粥样硬化，可能与调节性T细胞中FOXP3的高甲基化状态有关。

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来源期刊

Empirica ECONOMICS-

CiteScore

2.70

自引率

7.70%

发文量

期刊介绍： Empirica is a peer-reviewed journal, which publishes original research of general interest to an international audience. Authors are invited to submit empirical papers in all areas of economics with a particular focus on European economies. Per January 2021, the editors also solicit descriptive papers on current or unexplored topics. Founded in 1974, Empirica is the official journal of the Nationalökonomische Gesellschaft (Austrian Economic Association) and is published in cooperation with Austrian Institute of Economic Research (WIFO). The journal aims at a wide international audience and invites submissions from economists around the world. Officially cited as: Empirica