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Iranian Journal of Basic Medical Sciences، جلد ۲۸، شماره ۹، صفحات ۱۱۸۰-۱۱۸۹

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عنوان انگلیسی Adipose stem cell-derived exosomes circular RNA circFryl attenuate atrial fibrosis and cardiomyocyte apoptosis in atrial fibrillation
چکیده انگلیسی مقاله 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.
کلیدواژه‌های انگلیسی مقاله Atrial fibrillation, Exosomes, Mesenchymal stem cells, microRNAs, Tissue Inhibitor of metalloproteinase-4

نویسندگان مقاله | Chunpu Li
Department of Cardiology, Xinghua People’s Hospital Affiliated to Yangzhou University, Xinghua, Jiangsu 225700, China


| Jiuting Tan
Department of Cardiology, Xinghua People’s Hospital Affiliated to Yangzhou University, Xinghua, Jiangsu 225700, China


| Xintao Deng
Department of Cardiology, Xinghua People’s Hospital Affiliated to Yangzhou University, Xinghua, Jiangsu 225700, China



نشانی اینترنتی https://ijbms.mums.ac.ir/article_25951.html
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