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BRD4770 inhibits vascular smooth muscle cell proliferation via SUV39H2, but not EHMT2 to protect against neointima formation

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单位： [1]Division of Cardiothoracic and Vascular Surgery,Sino- Swiss Heart-Lung Transplantation Institute,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Minist of Education, Chinese Academy of Medical Sciences, Wuhan, China [3]Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China

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The behavior of vascular smooth muscle cells (VSMCs) contributes to the formation of neointima. We previously found that EHMT2 suppressed autophagy activation in VSMCs. BRD4770, an inhibitor of EHMT2/G9a, plays a critical role in several kinds of cancers. However, whether and how BRD4770 regulates the behavior of VSMCs remain unknown. In this study, we evaluate the cellular effect of BRD4770 on VSMCs by series of experiments in vivo and ex vivo. We demonstrated that BRD4770 inhibited VSMCs' growth by blockage in G2/M phase in VSMCs. Moreover, our results demonstrated that the inhibition of proliferation was independent on autophagy or EHMT2 suppression which we previous reported. Mechanistically, BRD4770 exhibited an off-target effect from EHMT2 and our further study reveal that the proliferation inhibitory effect by BRD4770 was associated with suppressing on SUV39H2/KTM1B. In vivo, BRD4770 was also verified to rescue VIH. Thus, BRD4770 function as a crucial negative regulator of VSMC proliferation via SUV39H2 and G2/M cell cycle arrest and BRD4770 could be a molecule for the therapy of vascular restenosis.© 2023. The Author(s).

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出版当年[2022]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学

最新[2025]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学

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出版当年[2021]版：

Q3 CELL BIOLOGY

最新[2023]版：

Q3 CELL BIOLOGY

影响因子： 3.4 最新[2023版] 3.4 最新五年平均 4.374 出版当年[2021版] 4.232 出版当年五年平均 4.174 出版前一年[2020版] 4.3 出版后一年[2022版]

第一作者：

第一作者单位： [1]Division of Cardiothoracic and Vascular Surgery,Sino- Swiss Heart-Lung Transplantation Institute,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China

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通讯作者：

通讯机构： [1]Division of Cardiothoracic and Vascular Surgery,Sino- Swiss Heart-Lung Transplantation Institute,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Minist of Education, Chinese Academy of Medical Sciences, Wuhan, China

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