MiR-449 improves cardiac function by regulating HDAC1 and cTnI

B. Yang, H. Zhao, R. Dong

Department of Cardiology, Chinese PLA General Hospital, Beijing, China. FengCaofengrao@163.com

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• Cardiology

OBJECTIVE: To investigate the effect of microRNA-449 (miRNA-449) on cTnI and cardiac function and reveal the mechanism of Histone deacetylase 1 (HDAC1)-mediated histone deacetylation in cardiomyocytes.

MATERIALS AND METHODS: First, we used biochemical analysis and Dual-Luciferase reporter gene assay to confirm that HDAC1 and miR-449 having the binding site. Then, the effect of miR-449 inhibited HDAC1 on cTnI gene transcription was observed. In vivo, the effect of histone acetylation on cTnI expression and cardiac function in heart was observed in elderly mice with low expression of cTnI through miR-449 agomiR intervention.

RESULTS: This study revealed miR-449 can sponge with HDAC1. HDAC1-mediated histone deacetylation was involved in the regulation of cTnI gene expression by HDAC1-mediated acetylation of H3K4 and H3K9 in cTnI promoter regions. In addition, HDAC1-mediated histone deacetylation regulated the binding of the transcription factor GATA4 to the GATA element in the cTnI promoter region and improved cardiac function in elderly mice with low expression of cTnI

CONCLUSIONS: MiR-449 can regulate the acetylation of the histones H3K4 and H3K9 of the GATA element in the cTnI promoter region, thereby recruiting the transcription factor GATA4 to the cTnI promoter region, upregulating the cTnI gene expression, and improving cardiac function in elderly mice with low expression of cTnI.

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