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LncRNA H19 suppresses pyroptosis of cardiomyocytes to attenuate myocardial infarction in a PBX3/CYP1B1-dependent manner

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Abstract

Objective

Myocardial infarction (MI) is a major cause of cardiovascular disease which poses great healthy and financial burden for individuals. MI can be mainly induced by hypoxia. Therefore, in this study, we aimed to explore the function and mechanism of lncRNA H19 on hypoxia-induced pyroptosis of cardiomyocytes.

Method

Peripheral blood from healthy controls and MI patients was collected for determination of mRNA and protein expression levels of H19 and CYP1B1. The correlation between these two factors was analyzed. Then MI rat model was established and injected with H19 overexpression/CYP1B1 knockdown plasmid, in which the infraction area and pathological morphology were observed. Hypoxic cardiomyocytes were transfected with overexpression or knockdown of H19 and CYP1B1 for determination of NLRP3, ASC, caspase-1, IL-1β, IL-18, CyclinD1, and PCNA. Cell proliferation ability was assessed by CCK8. RIP and dual luciferase gene reporter assay were applied to verify the binding among H19, PBX3 and CYP1B1.

Results

Downregulated H19 and upregulated CYP1B1 were observed in MI patients. A negative correlation was found for H19 and CYP1B1 expressions. Transfection of H19 overexpression or CYP1B1 knockdown could attenuate the MI progression in MI rats. In hypoxic cardiomyocytes, H19 overexpression or CYP1B1 knockdown could also inhibit NLRP3, ASC, caspase-1, IL-1β, and IL-18 in addition to suppressing cell apoptosis rate and promoting cell proliferation rate. Different expression pattern was found in cells transfected with H19 knockdown or CYP1B1 overexpression. Overexpression of CYP1B1 could abrogate the suppressive effect of H19 on pyroptosis of cardiomyocytes. H19 could inhibit activity of CYP1B1 promoters by regulating PBX3.

Conclusion

H19 could inhibit CYP1B1 expression in a PBX3-dependent way and thus attenuate cell pyroptosis of cardiomyocytes.

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Authors and Affiliations

  1. Department of Cardiology, Hunan Provincial People’s Hospital, Changsha, Hunan, 410005, People’s Republic of China

    Youjian Han, Bo Dong & Meijuan Chen

  2. No.3 Obstetrics and Gynecology Department, Hunan Provincial People’s Hospital, Changsha, Hunan, 410005, People’s Republic of China

    Chanjiao Yao

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Han, Y., Dong, B., Chen, M. et al. LncRNA H19 suppresses pyroptosis of cardiomyocytes to attenuate myocardial infarction in a PBX3/CYP1B1-dependent manner. Mol Cell Biochem 476, 1387–1400 (2021). https://doi.org/10.1007/s11010-020-03998-y

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