M1 巨噬细胞来源的细胞外囊泡通过抑制微小 RNA-185-3p 来加重载脂蛋白 E 小鼠动脉粥样硬化的发展

M1 macrophages-derived extracellular vesicles elevate microRNA-185-3p to aggravate the development of atherosclerosis in ApoE mice by inhibiting small mothers against decapentaplegic 7.

机构信息

Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, China.

出版信息

Int Immunopharmacol. 2021 Jan;90:107138. doi: 10.1016/j.intimp.2020.107138. Epub 2020 Dec 7.

DOI:10.1016/j.intimp.2020.107138

PMID:33302032

Abstract

OBJECTIVE

Extracellular vesicles (EVs) are vital mediators of transferring microRNAs (miRNAs). We focused on effect of miR-185-3p that mediated by macrophages-derived EVs on atherosclerosis (AS) by targeting small mothers against decapentaplegic 7 (Smad7).

METHODS

EVs were extracted from M1 macrophages and identified. ApoE mice were treated with EVs, EVs containing miR-185-3p inhibitor or mimic, then the pathological changes of mouse aorta were observed. The levels of blood lipid, cell adhesion molecules, oxidative stress factors, inflammatory factors, and proliferation and apoptosis of vascular endothelial cells were assessed. Expression of miR-185-3p and Smad7 was detected and the targeting relationship between miR-185-3p and Smad7 was validated.

RESULTS

MiR-185-3p was upregulated while Smad7 was downregulated in atherosclerotic mouse aorta. M1 macrophages-derived EVs elevated miR-185-3p to promote development of AS pathology and levels of blood lipid, endothelial cellular adhesion, oxidative stress factors and inflammatory factors, suppressed cell proliferation and promoted cell apoptosis of vascular endothelial cells in atherosclerotic mice through downregulating Smad7. Smad7 was a target gene of miR-185-3p and miR-185-3p could inhibit expression of Smad7.

CONCLUSION

M1 macrophages-derived EVs and upregulated miR-185-3p aggravated the development of AS in ApoE mice by negatively regulating Smad7. This research may further the understanding of AS mechanism.

摘要

目的

细胞外囊泡（EVs）是传递 microRNAs（miRNAs）的重要介质。我们专注于巨噬细胞衍生的 EVs 中 miR-185-3p 通过靶向 small mothers against decapentaplegic 7（Smad7）对动脉粥样硬化（AS）的影响。

方法

从 M1 巨噬细胞中提取 EVs 并进行鉴定。用 EVs、含 miR-185-3p 抑制剂或模拟物的 EVs 处理 apoE 小鼠，然后观察小鼠主动脉的病理变化。评估血脂、细胞黏附分子、氧化应激因子、炎症因子、血管内皮细胞的增殖和凋亡水平。检测 miR-185-3p 和 Smad7 的表达，并验证 miR-185-3p 和 Smad7 之间的靶向关系。

结果

在动脉粥样硬化小鼠的主动脉中，miR-185-3p 上调而 Smad7 下调。M1 巨噬细胞衍生的 EVs 上调 miR-185-3p 以促进 AS 病理的发展，并通过下调 Smad7 增加血脂、内皮细胞黏附、氧化应激因子和炎症因子水平，抑制血管内皮细胞增殖，促进其凋亡。Smad7 是 miR-185-3p 的靶基因，miR-185-3p 可抑制 Smad7 的表达。