Abstract
Cardiac diastolic dysfunction (CDD) is the most common form of cardiovascular disorders, especially in elderly people. Cardiac troponin I (cTnI) plays a critical role in the regulation of cardiac function, especially diastolic function. Our previous studies showed that cTnI‐low expression induced by histone acetylation modification might be one of the causes that result in diastolic dysfunction in ageing hearts. This study was designed to investigate whether epigallocatechin‐3‐gallate (EGCG) would modify histone acetylation events to regulate cTnI expression and then improve cardiac functions in ageing mice. Our study shows that EGCG improved cardiac diastolic function of aged mice after 8‐week treatment. Low expression of cTnI in the ageing hearts was reversed through EGCG treatment. EGCG inhibited the expression of histone deacetylase 1 (HDAC1) and HDAC3, and the binding levels of HDAC1 in the proximal promoter of cTnI. Acetylated lysine 9 on histone H3 (AcH3K9) levels of cTnI's promoter were increased through EGCG treatment. Additionally, EGCG resulted in an ascent of the binding levels of transcription factors GATA4 and Mef2c with cTnI's promoter. Together, our data indicate that EGCG may improve cardiac diastolic function of ageing mice through up‐regulating cTnI by histone acetylation modification. These findings provide new insights into histone acetylation mechanisms of EGCG treatment that may contribute to the prevention of CDD in ageing populations.
Highlights
Age-related changes in cardiovascular structure/function are implicated in the markedly increased risk for cardiovascular disease in older persons [1, 2]
Cardiac ageing is commonly associated with diastolic heart failure, which is referred to as heart failure with preserved ejection fraction (HFpEF)[24]
At least one study has reported that the content of Cardiac troponin I (cTnI) in left ventricular myocardial cells decreased in older men with or without cardiac disease [29]
Summary
Age-related changes in cardiovascular structure/function are implicated in the markedly increased risk for cardiovascular disease in older persons [1, 2]. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. Using a small sample of human heart tissues showed that the content of cTnI in LV myocardium may decrease in older men with or without cardiac disease. Our previous studies have demonstrated that progressive troponin I loss impairs cardiac relaxation and causes heart failure in mice [7], and our most recently published data showed that hypoacetylation of AcH3K9 near the key cis-elements of cTnI’s proximal promoter might cause a cTnI decrease in ageing hearts [8].
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