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LncRNA Rian reduces cardiomyocyte pyroptosis and alleviates myocardial ischemia–reperfusion injury by regulating by the miR-17-5p/CCND1 axis

Hypertension Research volume 45, pages 976–989 (2022)Cite this article

Abstract

Myocardial ischemia–reperfusion injury (MIRI) is a pathological process characterized by cardiomyocyte death. Long noncoding RNAs (lncRNAs) have been shown to be dysregulated in the course of MIRI. Accordingly, the current study investigated the mechanism of lncRNA Rian in MIRI-induced cardiomyocyte pyroptosis. First, a murine model of MIRI was established by using the left anterior descending (LAD) coronary artery ligation method. Cardiac function and myocardial histopathological changes were evaluated by echocardiography and hematoxylin and eosin staining. Then, a cell model of MIRI was established by oxygen-glucose deprivation/reoxygenation (OGD/R), followed by analysis of NLRP3, cleaved caspase-1, and GSDMD-N levels by western blotting. The levels of IL-1β, IL-18, TNF-α, and IL-10 were measured using ELISA. LncRNA Rian, miR-17-5p, and CCND1 expression in myocardial tissues and OGD/R cells were examined using RT-qPCR. Finally, the binding relationships between Rian and miR-17-5p and miR-17-5p and CCND1 were validated with the help of dual-luciferase and RNA pull-down assays. Rian was poorly expressed in MIRI mice and OGD/R cells. LncRNA Rian overexpression reduced cardiomyocyte pyroptosis in vivo and in vitro, as indicated by decreased NLRP3, cleaved caspase-1, GSDMD-N, IL-1β, IL-18, and TNF-α levels and increased IL-10 levels. Furthermore, Rian bound to miR-17-5p and promoted CCND1 transcription. Notably, miR-17-5p overexpression or CCND1 silencing reversed the inhibitory effect of Rian overexpression on cardiomyocyte pyroptosis. Collectively, our findings indicate that Rian overexpression reduces cardiomyocyte pyroptosis and alleviates MIRI through the miR-17-5p/CCND1 axis.

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Acknowledgements

We thank all of the members of our team for their excellent work.

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, Sichuan University West China Hospital, Chengdu, Sichuan Province, China

    Hui Kang, Hui Yu, Hao Ma & Ge Cao

  2. Department of Critical Care Medicine, Sichuan University West China Hospital, Chengdu, Sichuan Province, China

    Ling Zeng

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Correspondence to Ge Cao.

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The current study was approved by the Ethics Committee of Sichuan University West China Hospital. All animal experimental protocols complied with the Guide for the Care and Use of Laboratory Animals [44]. Extensive efforts were made to minimize the number and suffering of the experimental animals.

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Kang, H., Yu, H., Zeng, L. et al. LncRNA Rian reduces cardiomyocyte pyroptosis and alleviates myocardial ischemia–reperfusion injury by regulating by the miR-17-5p/CCND1 axis. Hypertens Res 45, 976–989 (2022). https://doi.org/10.1038/s41440-022-00884-6

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