Circ-Hipk3 in Adipose Derived Stem Cells Exosome Alleviates Myocardial Infarction Induced Myocardial Damage by Regulation miR-138-5p/Sirt1 Axis Mediated Autophagy.

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.