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Monday, November 30, 2020

miR-133a-3p attenuates cardiomyocyte hypertrophy through inhibiting pyroptosis activation by targeting IKKε.

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miR-133a-3p attenuates cardiomyocyte hypertrophy through inhibiting pyroptosis activation by targeting IKKε.

Acta Histochem. 2020 Nov 24;123(1):151653

Authors: Zhu YF, Wang R, Chen W, Cao YD, Li LP, Chen X

Abstract
OBJECTIVE: Cardiac hypertrophy is an adaptive response to physiological and pathological stimuli, the latter of which frequently progresses to valvulopathy, heart failure and sudden death. Recent reports revealed that pyroptosis is involved in regulating multiple cardiovascular diseases progression, including cardiac hypertrophy. However, the underlying mechanisms remain poorly understood. This study aims to extensively investigate the regulation of miR-133a-3p on pyroptosis in angiotensin II (Ang II)-induced cardiac hypertrophyin vitro.
METHODS: The in vitro model of cardiac hypertrophy was induced by Ang II, which was validated by qPCR combined with measurement of cell surface area by immunofluorescence assay. CCK-8 assay and Hochest33342/PI staining was performed to assess pyroptosis. Dual luciferase reporter system was used to verify the direct interaction between miR-133a-3p and IKKε. The effects of miR-133a-3p/IKKε on pyroptosis activation and cardiac hypertrophy markers (Caspase-1, NLRP3, IL-1β, IL-18, GSDMD, ASC, ANP, BNP and β-MHC) were evaluated by western blot, ELISA and qPCR.
RESULTS: Ang II treatment could induce cardiomyocyte hypertrophy and pyroptosis. The expression of miR-133a-3p was repressed in Ang II-treated HCM cells, and its overexpression could attenuate both pyroptosis and cardiac hypertrophyin vitro. Additionally, IKKε expression was significantly up-regulated in Ang II-induced HCM cells. Dual luciferase reporter system and qPCR validated that miR-133a-3p directly targeted the 3'-UTR of IKKε and suppressed its expression. Moreover, IKKε overexpression impaired the protective function of miR-133a-3p in cardiomyocyte hypertrophy.
CONCLUSION: Collectively, miR-133a-3p attenuates Ang II induced cardiomyocyte hypertrophy via inhibition of pyroptosis by targeting IKKε. Therefore, miR-133a-3p up-regulation may be a promising strategy for cardiac hypertrophy treatment.

PMID: 33246224 [PubMed - as supplied by publisher]

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