Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>This study reveals that the engineering of EVs derived from MenSCs holds significant promise as a strategic clinical approach for addressing inflammatory atherosclerosis.</p>

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

  • 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

摘要

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.