EGCG elevates wild-type cTnI expression in a cTnI-R193H mouse model of restrictive cardiomyopathy

doi:10.12092/j.issn.1009-2501.2019.04.003

Abstract

Abstract:

AIM: To increase the expression level of normal cTnI in mice with cTnIR193H restricted cardiomyopathy by EGCG. METHODS: 8 weeks old wild type C57 mice and 8 weeks old cTnIR193H restricted cardiomyopathy model mice were randomly divided into EGCG intervention, DMSO intervention group and non intervention group. After 5 days of intervention, the heart tissues of mice were collected after 3 months. mRNA expression levels of HDAC1, GATA4 and cTnI were detected by Western blot and RT-PCR respectively. The acetylation level of histone H3K9, the binding level of GATA4 and HDAC1 in cTnI gene promoter region were detected by ChIP-Q-PCR. RESULTS:The level of protein level in the EGCG intervention group and the expression of normal cTnI at the level of mRNA, the level of mRNA expression of GATA4, the level of histone H3K9 acetylation, and the binding level of GATA4 were higher than those of the unpretreated group (P<0.05). The level of HDAC1 binding and HDAC1 mRNA expression level in cTnI promoter region were lower than those in the non intervention group (P<0.05). CONCLUSION: In the R193H model mice, EGCG inhibits the expression of HDAC1 and inhibits the binding of HDAC1 in the promoter region of cTnI, thus promoting the expression of cardiac transcription factor GATA4, the acetylation of histone H3K9, and the combination of GATA4 in the promoter region of cTnI, and up regulation of the cTnI expression of myocardium.

Key words: (-)-epigallo-catechin-3-gallate, cardiac diastolic dysfunction, restrictive cardiomyopathy, cTnI, histone acetylation

CLC Number:

R965.2

ZHANG Mingqing，LIU Lingjuan，TIAN Jie. EGCG elevates wild-type cTnI expression in a cTnI-R193H mouse model of restrictive cardiomyopathy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(4): 376-382.

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