Yang Guoxun, Nong Danpeng, Tang Xiao, Tan Ling, Yang Peng, Ning Haien
Institute of Hypertension Vascular Disease, Guangxi International Zhuang Medicine Hospital, No.8 Qiuyue Road, Wuxiang New District, Nanning, 530201, Guangxi, China.
Department of Cardiology, Guangxi International Zhuang Medicine Hospital, Nanning, Guangxi, China.
Biochem Genet. 2025 Jul 23. doi: 10.1007/s10528-025-11173-5.
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.
心肌梗死（MI）是一个重大的健康问题，也是全球范围内的主要死因。大量研究证实，干细胞来源的外泌体已被证明能有效修复心肌梗死损伤诱导的心肌细胞损伤。然而，脂肪组织来源的间充质干细胞（ADSC）-外泌体的心脏保护作用仍不清楚。本研究旨在探讨ADSC来源的外泌体对心肌梗死治疗小鼠心脏的保护作用，并探索其潜在机制。使用培养的ADSCs研究细胞和分子机制。在C57BL/6 J小鼠上，我们建立了心肌梗死模型。使用HMEC-1来确定调节机制。ELISA用于检测炎症因子表达。荧光素酶报告分析检测显示了miR-138-5p、Sirt1和circ-Hipk3之间的关系。ADSCs外泌体治疗通过促进自噬和抑制炎症反应显著减轻心肌梗死诱导的心肌损伤。Circ-Hipk3在ADSCs外泌体介导的对心肌梗死诱导的心肌损伤的保护作用中起重要作用。荧光素酶报告分析证实miR-138-5p和SIRT1在circ-Hipk3下游。下调SIRT1或上调miR-138-5p可逆转circ-Hipk3对自噬和炎症因子表达的调节作用。过表达circ-Hipk3增强了ADSC-Exo对心肌梗死诱导的心肌损伤的保护作用。总之，这些发现表明，ADSC-Exos中的circ-Hipk3可通过miR-138-5p/Sirt1轴介导的自噬信号通路减轻心肌梗死治疗小鼠的心脏损伤。含有circ-Hipk3的ADSC-Exos在心肌梗死诱导的心脏损伤中具有广阔的治疗潜力。
