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MiR-568 mitigated cardiomyocytes apoptosis, oxidative stress response and cardiac dysfunction via targeting SMURF2 in heart failure rats

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Abstract

Chronic heart failure (CHF), a conventional, complex, and severe syndrome, is generally defined by myocardial output inadequate to satisfy the metabolic requirements of body tissues. Recently, miR-568 was identified to be down-regulated in CHF patients’ sera and negatively correlated with left ventricular mass index in symptomatic CHF patients with systolic dysfunction. Nevertheless, the role of miR-568 during CHF development remains obscure. The current study is aimed to investigate the role of miR-568 in CHF. The MTT assay, flow cytometry analysis, RT-qPCR analysis, western blot analysis and luciferase reporter assays were conducted to figure out the function and potential mechanism of miR-568 in vitro. Rats were operated with aortic coarctation to establish CHF animal model. The effects of miR-568 and SMURF2 on CHF rats were evaluated by hematoxylin–eosin staining, Masson’s staining, serum index testing, cardiac ultrasound detection, and TUNEL staining assays. We discovered that miR-568 level was downregulated by H2O2 treatment in cardiomyocytes. In mechanism, miR-568 directly targeted and negatively regulated SMURF2. In function, SMURF2 overexpression reversed the effects of miR-568 on cardiac function and histological changes in vivo. Additionally, SMURF2 overexpression reversed the effects of miR-568 on the content of LDH, AST, CK and CK-MB in vivo. Moreover, SMURF2 overexpression reversed the effects of miR-568 on oxidative stress response in vivo. MiR-568 mitigated cardiomyocytes apoptosis, oxidative stress response and cardiac dysfunction via targeting SMURF2 in CHF rats. This discovery may serve as a potential biomarker for CHF treatment.

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  1. Qian Zhang and Jun Yin authors contributed equally to the work.

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  1. Department of Cardiology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, No. 168, Hong Kong Road, Jiang’an District, Wuhan, 430015, Hubei, China

    Qian Zhang, Jun Yin & Yong Zou

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Zhang, Q., Yin, J. & Zou, Y. MiR-568 mitigated cardiomyocytes apoptosis, oxidative stress response and cardiac dysfunction via targeting SMURF2 in heart failure rats. Heart Vessels 38, 857–868 (2023). https://doi.org/10.1007/s00380-022-02231-8

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