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Published on: July 10, 2019
Circ-Hipk3 in Adipose Derived Stem Cells Exosome Alleviates Myocardial Infarction Induced Myocardial Damage by
Guoxun Yang1, Danpeng Nong2, Xiao Tang3
1Institute of Hypertension Vascular Disease, Guangxi International Zhuang Medicine Hospital, No.8 Qiuyue Road, Wuxiang New District, Nanning, 530201, Guangxi, China. gnygxdt@163.com.
Insights
Adipose tissue-derived mesenchymal stem cell exosomes (ADSC-Exos) show therapeutic potential for myocardial infarction (MI). ADSC-Exos containing circ-Hipk3 protect against cardiac injury by modulating the miR-138-5p/Sirt1 pathway and autophagy.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Molecular Biology
Background:
- Myocardial infarction (MI) is a leading cause of death globally.
- Stem cell-derived exosomes show promise in repairing MI-induced heart damage.
- The cardioprotective role of adipose tissue-derived mesenchymal stem cell exosomes (ADSC-Exos) requires further elucidation.
Purpose of the Study:
- To investigate the protective effects of ADSC-Exos on myocardial injury in a mouse model of MI.
- To explore the underlying molecular mechanisms, focusing on the role of circ-Hipk3, miR-138-5p, and Sirt1.
Main Methods:
- Establishment of a myocardial infarction (MI) model in C57BL/6J mice.
- Investigation of cellular and molecular mechanisms using cultured ADSCs and HMEC-1 cells.
- Analysis of inflammatory factors via ELISA and molecular interactions using luciferase reporter assays.
Main Results:
- ADSC-Exos treatment significantly alleviated MI-induced myocardial damage by promoting autophagy and inhibiting inflammation.
- Circ-Hipk3 plays a crucial role in the protective effects of ADSC-Exos.
- The miR-138-5p/Sirt1 axis was identified downstream of circ-Hipk3, mediating autophagy and inflammatory responses.
Conclusions:
- ADSC-Exos protect against cardiac injury in MI through the circ-Hipk3/miR-138-5p/Sirt1 axis, modulating autophagy signaling.
- Circ-Hipk3 within ADSC-Exos demonstrates significant therapeutic potential for treating MI-induced cardiac injury.
Abstract:
Myocardial infarction (MI) is a major health problem and is the leading cause of death worldwide. Accumulation studies confirm that exosomes derived from stem cells have been shown to effectively repair MI injury-induced cardiomyocyte damage. However, the cardioprotective benefits of adipose tissue-derived mesenchymal stem cell (ADSC)-Exos remain unclear. This study aimed to investigate the protective effects of exosomes from ADSC on the hearts of MI-treated mice and to explore the underlying mechanisms. Cellular and molecular mechanisms were investigated using cultured ADSCs. On C57BL/6 J mice, we performed myocardial MI model. HMEC-1 was used to identify the regulatory mechanism. ELISA was used for inflammatory factor expression detection. Luciferase report analysis detection showed the relationship among miR-138-5p, Sirt1 and circ-Hipk3. ADSCs exosome treatment significantly alleviates MI induced myocardial damage by promotion autophagy and inhibits inflammatory response. Circ-Hipk3 play an important role in ADSCs exosome mediated protective effect on MI induced myocardial damage. Luciferase report analysis confirmed that miR-138-5p and SIRT1 were at circ-Hipk3 downstream. Downregulation SIRT1 or upregulation miR-138-5p reversed the regulation effect of circ-Hipk3 on autophagy and inflammatory factor expression. Overexpression circ-Hipk3 increased the protective effect of ADSC-Exo on MI induced myocardial damage. In summary, these findings show that circ-Hipk3 from ADSC-Exos can alleviate cardiac injury in MI-treated mice via the miR-138-5p/Sirt1 axis mediated autophagy signaling pathway. ADSC-Exos containing circ-Hipk3 has a promising therapeutic potential in MI induced cardiac injury.
