Arterial Occlusive Disease | MicroRNA-205-5p Promotes Unstable Atherosclerotic Plaque Formation In Vivo | springermedicine.com

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Cardiovascular Drugs and Therapy

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01-02-2020 | Arterial Occlusive Disease | Original Article

MicroRNA-205-5p Promotes Unstable Atherosclerotic Plaque Formation In Vivo

Authors: Xiandong Meng, Jianjiao Yin, Xinli Yu, Yonggang Guo

Published in: Cardiovascular Drugs and Therapy | Issue 1/2020

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Abstract

Purpose

Atherosclerosis is a narrowing of the arteries caused by plaque buildup. MicroRNAs (miRNAs) have been proposed to participate in the pathogenesis of atherosclerosis. Here, we aimed to investigate miR-205-5p’s role in promoting atherosclerotic progression.

Methods

Knock-in (KI) mice with human/murine miR-205-5p within the murine host gene for miR-205 (MIR205HG) were crossed with apolipoprotein E knockout (Apoe^−/−) mice. This miR-205KI Apoe^−/− murine model was employed to study the impact of miR-205-5p in Apoe^−/− mice susceptible to atherosclerotic plaque formation.

Results

miR-205KI Apoe^−/−mice developed larger, more unstable plaques relative to their Apoe^−/− counterparts (0.45 vs. 0.26 mm², P < 0.001). miR-205KI Apoe^−/− mice exhibited lower serum levels of high-density lipoprotein cholesterol (HDL-C) (5.18 vs. 19.31 mg/dL, P < 0.001) and triglycerides (32.79 vs. 156.76 mg/dL, P < 0.001) with system-wide reversal of cholesterol transport. Macrophages derived from miR-205KI Apoe^−/− mice exhibited ~ 20% lowered cholesterol efflux capability with enhanced pro-inflammatory gene expression through lipid raft formation. Bone marrow transplantation demonstrated that bone marrow (BM) donor cells with miR-205-5pKI simulated plaque formation independent of the recipients’ miR-205-5p status.

Conclusions

miR-205-5p encourages unstable atherogenesis in vivo. miR-205-5p also adversely influences lipid metabolism and promotes a pro-inflammatory macrophage phenotype. Our findings advocate miR-205-5p as a potential therapeutic target for combating unstable atherogenesis.

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Title: MicroRNA-205-5p Promotes Unstable Atherosclerotic Plaque Formation In Vivo
Authors: Xiandong Meng
Jianjiao Yin
Xinli Yu
Yonggang Guo
Publication date: 01-02-2020
Publisher: Springer US
Keyword: Arterial Occlusive Disease
Published in: Cardiovascular Drugs and Therapy / Issue 1/2020
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-020-06935-9

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