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微小RNA-342-5p的下调或Wnt3a的上调抑制动脉粥样硬化小鼠的血管生成并维持动脉粥样硬化斑块稳定性。

Down-regulation of microRNA-342-5p or Up-regulation of Wnt3a Inhibits Angiogenesis and Maintains Atherosclerotic Plaque Stability in Atherosclerosis Mice.

作者信息

Sun Haixia, Feng Jinhua, Ma Yan, Cai Ding, Luo Yulu, Wang Qinggong, Li Fang, Zhang Mingyue, Hu Quanzhong

机构信息

Department of Cardiac Ultrasound, Qinghai Provincial People's Hospital, Xining, 810007, Qinghai Province, China.

Department of General Practitioner, Qinghai Provincial People's Hospital, Xining, 810007, Qinghai, China.

出版信息

Nanoscale Res Lett. 2021 Nov 22;16(1):165. doi: 10.1186/s11671-021-03608-w.

DOI:10.1186/s11671-021-03608-w
PMID:34807315
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8609054/
Abstract

Evidence has demonstrated that microRNA-342-5p (miR-342-5p) is implicated in atherosclerosis (AS), but little is known regarding its intrinsic regulatory mechanisms. Here, we aimed to explore the effect of miR-342-5p targeting Wnt3a on formation of vulnerable plaques and angiogenesis of AS. ApoE mice were fed with high-fat feed for 16 w to replicate the AS vulnerable plaque model. miR-342-5p and Wnt3a expression in aortic tissues of AS were detected. The target relationship between miR-342-5p and Wnt3a was verified. Moreover, ApoE mice were injected with miR-342-5p antagomir and overexpression-Wnt3a vector to test their functions in serum lipid levels, inflammatory and oxidative stress-related cytokines, aortic plaque stability and angiogenesis in plaque of AS mice. miR-342-5p expression was enhanced and Wnt3a expression was degraded in aortic tissues of AS mice and miR-342-5p directly targeted Wnt3a. Up-regulating Wnt3a or down-regulating miR-342-5p reduced blood lipid content, inflammatory and oxidative stress levels, the vulnerability of aortic tissue plaque and inhibited angiogenesis in aortic plaque of AS mice. Functional studies show that depleting miR-342-5p can stabilize aortic tissue plaque and reduce angiogenesis in plaque in AS mice via restoring Wnt3a.

摘要

已有证据表明,微小RNA-342-5p(miR-342-5p)与动脉粥样硬化(AS)有关,但其内在调控机制尚不清楚。在此,我们旨在探讨miR-342-5p靶向Wnt3a对AS易损斑块形成和血管生成的影响。给载脂蛋白E(ApoE)小鼠喂食高脂饲料16周以复制AS易损斑块模型。检测AS小鼠主动脉组织中miR-342-5p和Wnt3a的表达。验证miR-342-5p与Wnt3a之间的靶向关系。此外,给ApoE小鼠注射miR-342-5p拮抗剂和Wnt3a过表达载体,以测试它们在AS小鼠血脂水平、炎症和氧化应激相关细胞因子、主动脉斑块稳定性及斑块血管生成方面的作用。AS小鼠主动脉组织中miR-342-5p表达增强,Wnt3a表达降低,且miR-342-5p直接靶向Wnt3a。上调Wnt3a或下调miR-342-5p可降低血脂含量、炎症和氧化应激水平、主动脉组织斑块的易损性,并抑制AS小鼠主动脉斑块中的血管生成。功能研究表明,通过恢复Wnt3a,消耗miR-342-5p可稳定AS小鼠的主动脉组织斑块并减少斑块中的血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/cbb6268faf35/11671_2021_3608_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/bad2666013fa/11671_2021_3608_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/40fd877005c6/11671_2021_3608_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/7116e7b3c9c0/11671_2021_3608_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/8c7b3fd7f7d9/11671_2021_3608_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/5fc88cd8bef0/11671_2021_3608_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/cbb6268faf35/11671_2021_3608_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/bad2666013fa/11671_2021_3608_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/40fd877005c6/11671_2021_3608_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/7116e7b3c9c0/11671_2021_3608_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/8c7b3fd7f7d9/11671_2021_3608_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/5fc88cd8bef0/11671_2021_3608_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e782/8609054/cbb6268faf35/11671_2021_3608_Fig6_HTML.jpg

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