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High glucose promotes atherosclerosis by regulating miRNA let7d‐5p level
Journal of Diabetes Investigation ( IF 3.1 ) Pub Date : 2024-03-14 , DOI: 10.1111/jdi.14180 Hua Wang 1 , Fentao Liu 2 , Wenyu Zhao 3 , Yiting Guo 3 , Peipei Mai 1 , Songfeng Zhao 4 , Zhiguo Wen 4 , Jie Su 3 , Xuan Li 3 , Yunlong Wang 5, 6 , Yanfang Zhang 3, 6
Journal of Diabetes Investigation ( IF 3.1 ) Pub Date : 2024-03-14 , DOI: 10.1111/jdi.14180 Hua Wang 1 , Fentao Liu 2 , Wenyu Zhao 3 , Yiting Guo 3 , Peipei Mai 1 , Songfeng Zhao 4 , Zhiguo Wen 4 , Jie Su 3 , Xuan Li 3 , Yunlong Wang 5, 6 , Yanfang Zhang 3, 6
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BackgroundMiRNA let7d‐5p has been recently reported to be abnormally expressed in diabetes‐associated atherosclerosis (AS). However, it still remains unknown how let7d‐5p contributes to the process of atherosclerosis.MethodsTwenty fresh tissues and a total of 28 wax block specimens from carotid endarterectomy procedures were obtained from the Luoyang Central Hospital affiliated to Zhengzhou University. The expression of let7d‐5p was assessed using quantitative RT‐PCR (qRT‐PCR). A series of in vitro experiments was used to determine the roles of let7d‐5p knockdown and overexpression in vascular smooth muscle cells (VSMCs).ResultsWe discovered that the carotid plaques from diabetic patients had lower expression levels of miR let7d‐5p. In VSMCs, the expression of miRNA let7d‐5p was significantly lower in high glucose conditions compared with low glucose situations. The proliferation and migration of VSMCs were also inhibited by the overexpression of let7d‐5p, whereas the opposite was true when let7d‐5p was inhibited, according to gain and loss of function studies. Mechanically, let7d‐5p might activate the GSK3β/β‐catenin signaling pathway via binding to the high mobility group AT‐Hook 2 (HMGA2) mRNA in VSMCs. Additionally, GLP‐1RA liraglutide may prevent the migration and proliferation of VSMCs by raising let7d‐5p levels.ConclusionsHigh glucose stimulated the proliferation and migration of VSMCs by regulating the let7d‐5p/HMGA2/GSK3β/β‐catenin pathway, and liraglutide may slow atherosclerosis by increasing the levels of miR let7d‐5p.
中文翻译：
高糖通过调节miRNA let7d-5p水平促进动脉粥样硬化
背景 最近有报道称 MiRNA let7d-5p 在糖尿病相关动脉粥样硬化 (AS) 中异常表达。然而let7d-5p如何参与动脉粥样硬化的进程仍不清楚。方法取自郑州大学附属洛阳市中心医院颈动脉内膜剥脱术的20例新鲜组织和共28块蜡块标本。使用定量 RT-PCR (qRT-PCR) 评估 let7d-5p 的表达。一系列体外实验用于确定let7d-5p敲低和过表达在血管平滑肌细胞（VSMC）中的作用。结果我们发现糖尿病患者的颈动脉斑块中miR let7d-5p的表达水平较低。在 VSMC 中，与低糖条件下相比，高糖条件下 miRNA let7d-5p 的表达显着降低。根据功能获得和丧失的研究，let7d-5p 的过度表达也会抑制 VSMC 的增殖和迁移，而当 let7d-5p 受到抑制时，情况恰恰相反。从机械角度来说，let7d-5p 可能通过与 VSMC 中的高迁移率基团 AT-Hook 2 (HMGA2) mRNA 结合来激活 GSK3β/β-catenin 信号通路。此外，GLP-1RA利拉鲁肽可能通过提高let7d-5p水平来阻止VSMCs的迁移和增殖。结论高糖通过调节let7d-5p/HMGA2/GSK3β/β-catenin通路刺激VSMCs的增殖和迁移，利拉鲁肽可能会减缓VSMCs的增殖和迁移。通过增加 miR let7d-5p 的水平来预防动脉粥样硬化。
更新日期：2024-03-14
中文翻译：
高糖通过调节miRNA let7d-5p水平促进动脉粥样硬化
背景 最近有报道称 MiRNA let7d-5p 在糖尿病相关动脉粥样硬化 (AS) 中异常表达。然而let7d-5p如何参与动脉粥样硬化的进程仍不清楚。方法取自郑州大学附属洛阳市中心医院颈动脉内膜剥脱术的20例新鲜组织和共28块蜡块标本。使用定量 RT-PCR (qRT-PCR) 评估 let7d-5p 的表达。一系列体外实验用于确定let7d-5p敲低和过表达在血管平滑肌细胞（VSMC）中的作用。结果我们发现糖尿病患者的颈动脉斑块中miR let7d-5p的表达水平较低。在 VSMC 中，与低糖条件下相比，高糖条件下 miRNA let7d-5p 的表达显着降低。根据功能获得和丧失的研究，let7d-5p 的过度表达也会抑制 VSMC 的增殖和迁移，而当 let7d-5p 受到抑制时，情况恰恰相反。从机械角度来说，let7d-5p 可能通过与 VSMC 中的高迁移率基团 AT-Hook 2 (HMGA2) mRNA 结合来激活 GSK3β/β-catenin 信号通路。此外，GLP-1RA利拉鲁肽可能通过提高let7d-5p水平来阻止VSMCs的迁移和增殖。结论高糖通过调节let7d-5p/HMGA2/GSK3β/β-catenin通路刺激VSMCs的增殖和迁移，利拉鲁肽可能会减缓VSMCs的增殖和迁移。通过增加 miR let7d-5p 的水平来预防动脉粥样硬化。
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