Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation
Objective(s): Atrial fibrillation (AF) is a prevalent arrhythmia accompanied by structural and electrical remodeling of the heart. Here, we examined the possible mechanisms behind the protective role of adipose-derived stem cell (ADSC)-derived exosomes in AF therapy.Materials and Methods: We isolate...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Mashhad University of Medical Sciences
2025-09-01
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| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | https://ijbms.mums.ac.ir/article_25951_de6cf63780fa12f8740dee3e64c4b5cd.pdf |
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| Summary: | Objective(s): Atrial fibrillation (AF) is a prevalent arrhythmia accompanied by structural and electrical remodeling of the heart. Here, we examined the possible mechanisms behind the protective role of adipose-derived stem cell (ADSC)-derived exosomes in AF therapy.Materials and Methods: We isolated exosomes from ADSCs. Exosome treatment was given. The left atrial diameter was measured by echocardiographic imaging. Cardiac fibrosis and damage were detected. The interaction between miR-338-3p with circFryl and tissue inhibitor of metalloproteinase mRNA (4TIMP4 mRNA) was predicted and investigated using qPCR and western blotting assay. Results: The overexpression of circFryl in ADSCs elevated the level of circFryl in exosomes and the myocytes, whereas knockdown of circFryl exhibited the opposite effects. Treatment with ADSC-exosomes significantly elevated circFryl level and recovered left atrial diameter, whereas knockdown of circFryl in exosomes abolished these effects. ADSC-exosomes alleviated the cardiac fibrosis and cell apoptosis in the AF model, and the knockdown of circFryl abolished these effects. ADSC-exosomes treatment suppressed viability and fibrosis and enhanced cell apoptosis in Ang-II-induced fibroblasts, which was reversed by depletion of circFryl. Online analysis of miRNA interaction targets showed potential binding between miR-338-3p with circFryl and TIMP4 mRNA. Knockdown of circFryl notably suppressed TIMP4 level, and inhibition of miR-338-3p recovered TIMP4 level. TIMP4 overexpression and miR-338-3p inhibition abolished the effects of sicircFryl in vitro and in vivo. Conclusion: The ADSC-derived exosomes delivered circFryl to interact with miR-338-3p, subsequently enhancing TIMP4 mRNA stability and expression in cardiac fibroblasts and myocytes. The circFryl/miR-338-3p/TIMP4 axis mediated the protective effects of ADSC on AF. |
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| ISSN: | 2008-3866 2008-3874 |