Extracellular vesicles derived from menstrual blood-derived mesenchymal stem cells suppress inflammatory atherosclerosis by inhibiting NF-κB signaling.

IF 8.3 1区医学 Q1 MEDICINE, GENERAL & INTERNAL

BMC Medicine Pub Date : 2025-10-15 DOI:10.1186/s12916-025-04390-7

Jinjin Yu, Xiaotian Liu, Lele Jin, Han Li, Suhui Wang, Yongwei Yang, Xilian Chen, Hongxia Wang, Yingke Li, Jie Lian, Chao Shi, Haihui Li, Yong Zhang, Emmanuel Jairaj Moses, Hongxing Zhang, Chunfu Zheng, Xinxing Zhu

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引用次数: 0

Abstract

Background: Numerous studies have highlighted the beneficial effects of mesenchymal stem cells (MSCs) in various inflammatory disorders. However, the regulatory role of MSCs in inflammatory atherosclerosis and the molecular mechanisms underlying their anti-inflammatory properties have largely remained elusive.

Methods: Differential ultracentrifugation was performed to isolate extracellular vesicles (EVs) released by menstrual blood-derived mesenchymal stem cells (MenSCs). An ApoE knockout atherosclerotic animal model was employed to investigate the regulatory effect of MenSC-EVs on inflammatory atherosclerosis. miRNA microarray screening analyses were conducted to identify potential effectors in MenSC-EVs that play a key role in the suppression of atherosclerosis mediated by the EVs.

Results: We demonstrated the remarkable potential of MenSC-EVs in alleviating atherosclerosis through the NF-κB signaling pathway. miR-574-5p serves as a crucial effector molecule transported by MenSC-EVs, suppressing endothelial inflammation and promoting nitric oxide production. This regulation contributes to the attenuation of atherosclerosis by regulating the abundance of c-Rel. The miR-574-5p/c-Rel axis shows significant clinical relevance to atherosclerosis.

Conclusions: This study reveals that the engineering of EVs derived from MenSCs holds significant promise as a strategic clinical approach for addressing inflammatory atherosclerosis.

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经血源性间充质干细胞细胞外囊泡通过抑制NF-κB信号传导抑制炎症性动脉粥样硬化。

背景：大量研究强调了间充质干细胞（MSCs）在各种炎症疾病中的有益作用。然而，MSCs在炎症性动脉粥样硬化中的调节作用及其抗炎特性的分子机制在很大程度上仍然是未知的。方法：采用差示超离心分离经血源性间充质干细胞（MenSCs）释放的细胞外囊泡（ev）。采用ApoE敲除动脉粥样硬化动物模型，研究mensc - ev对炎症性动脉粥样硬化的调节作用。我们进行了miRNA微阵列筛选分析，以确定mensc - ev中在ev介导的动脉粥样硬化抑制中发挥关键作用的潜在效应物。结果：我们证明了mensc - ev通过NF-κB信号通路缓解动脉粥样硬化的显著潜力。miR-574-5p是mensc - ev运输的关键效应分子，可抑制内皮炎症并促进一氧化氮的产生。这种调节通过调节c-Rel的丰度有助于动脉粥样硬化的衰减。miR-574-5p/c-Rel轴与动脉粥样硬化具有显著的临床相关性。结论：这项研究表明，从MenSCs中提取的EVs工程作为治疗炎症性动脉粥样硬化的战略性临床方法具有重要的前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Medicine 医学-医学：内科

CiteScore

13.10

自引率

1.10%

发文量

435

审稿时长

4-8 weeks

期刊介绍： BMC Medicine is an open access, transparent peer-reviewed general medical journal. It is the flagship journal of the BMC series and publishes outstanding and influential research in various areas including clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. In addition to research articles, the journal also publishes stimulating debates, reviews, unique forum articles, and concise tutorials. All articles published in BMC Medicine are included in various databases such as Biological Abstracts, BIOSIS, CAS, Citebase, Current contents, DOAJ, Embase, MEDLINE, PubMed, Science Citation Index Expanded, OAIster, SCImago, Scopus, SOCOLAR, and Zetoc.