当前位置: X-MOL 学术Cardiovasc. Toxicol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
miR-33a-5p Suppresses ox-LDL-Stimulated Calcification of Vascular Smooth Muscle Cells by Targeting METTL3
Cardiovascular Toxicology ( IF 3.4 ) Pub Date : 2021-05-24 , DOI: 10.1007/s12012-021-09663-0
Ruimei Han 1 , Jian Luo 2 , Lingpeng Wang 3 , Li Li 4 , Hongchao Zheng 1
Affiliation  

Oxidized low-density lipoprotein (ox-LDL) accumulation in the vascular wall plays a pivotal role in the development of atherosclerosis and vascular calcification. However, few studies focus on the regulatory roles of microRNAs in ox-LDL stimulated vascular calcification. The aim of the present study was to investigate how miR-33a-5p regulated vascular calcification stimulated by ox-LDL. In the present study, miR-33a-5p was downregulated during vascular smooth muscle cells (VSMCs) calcification and upon ox-LDL treatment. ox-LDL significantly stimulated VSMCs calcification, while miR-33a-5p overexpression by its mimics transfection inhibited alkaline phosphatase (ALP) activity, mineralization and marker genes associated with VSMCs calcification even in the presence of ox-LDL. Methyltransferase like 3 (METTL3) was the target gene of miR-33a-5p. METTL3 was upregulated during VSMCs calcification and upon ox-LDL treatment. When VSMCs were transfected with miR-33a-5p mimics, METTL3 was downregulated. METTL3 downregulation by siRNA method decreased VSMCs calcification even in the presence of ox-LDL. Taken together, these results suggest miR-33a-5p suppresses VSMCs calcification stimulated by ox-LDL via targeting METTL3, highlighting the critical role of miR-33a-5p/METTL3 in vascular calcification.



中文翻译:

miR-33a-5p 通过靶向 METTL3 抑制 ox-LDL 刺激的血管平滑肌细胞钙化

血管壁中氧化的低密度脂蛋白 (ox-LDL) 积累在动脉粥样硬化和血管钙化的发展中起关键作用。然而,很少有研究关注 microRNA 在 ox-LDL 刺激的血管钙化中的调节作用。本研究的目的是研究 miR-33a-5p 如何调节 ox-LDL 刺激的血管钙化。在本研究中,miR-33a-5p 在血管平滑肌细胞 (VSMC) 钙化和 ox-LDL 治疗期间下调。ox-LDL显着刺激VSMCs钙化,而miR-33a-5p通过其模拟转染抑制碱性磷酸酶(ALP)活性、矿化和与VSMCs钙化相关的标记基因,即使在ox-LDL存在下也是如此。甲基转移酶样3(METTL3)是miR-33a-5p的靶基因。在 VSMC 钙化和 ox-LDL 治疗期间,METTL3 上调。当用 miR-33a-5p 模拟物转染 VSMC 时,METTL3 被下调。即使在 ox-LDL 存在的情况下,通过 siRNA 方法下调 METTL3 也可降低 VSMC 钙化。总之,这些结果表明 miR-33a-5p 通过靶向 METTL3 抑制 ox-LDL 刺激的 VSMC 钙化,突出了 miR-33a-5p/METTL3 在血管钙化中的关键作用。

更新日期:2021-05-24
down
wechat
bug