Epigallocatechin gallate reverses cTnI-low expression-induced age-related heart diastolic dysfunction through histone acetylation modification.
Epigallocatechin gallate reverses cTnI-low expression-induced age-related heart diastolic dysfunction through histone acetylation modification.
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表没食子儿茶素没食子酸酯通过组蛋白乙酰化修饰逆转 cTnI 低表达诱导的年龄相关心脏舒张功能障碍
DOI：
10.1111/jcmm.13169
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发表时间：
2017-10
影响因子：
5.3
通讯作者：
Tian J
中科院分区：
文献类型：
--
作者：
Pan B;Quan J;Liu L;Xu Z;Zhu J;Huang X;Tian J
心脏舒张功能障碍（CDD）是心血管疾病中最常见的形式，尤其是在老年人中。心肌肌钙蛋白I（cTnI）在心脏功能尤其是舒张功能的调节中起着重要作用。我们前期的研究表明，组蛋白乙酰化修饰诱导cTnI低表达可能是导致衰老心脏舒张功能障碍的原因之一。本研究旨在研究表没食子儿茶素没食子酸酯（epigallocatechin-3-gallate，EGCG）是否会改变组蛋白乙酰化事件以调节cTnI表达，从而改善衰老小鼠的心脏功能。我们的研究表明，EGCG在8周治疗后改善了老年小鼠的心脏舒张功能。通过EGCG治疗，衰老心脏中cTnI的低表达被逆转。EGCG抑制组蛋白去乙酰化酶1（HDAC 1）和HDAC 3的表达，并抑制HDAC 1在cTnI近端启动子的结合水平。通过EGCG处理，cTnI启动子组蛋白H3上的乙酰化赖氨酸9（AcH 3 K9）水平增加。此外，EGCG还能提高转录因子GATA 4和Mef 2c与cTnI启动子的结合水平。总之，我们的数据表明，EGCG可以通过组蛋白乙酰化修饰上调cTnI来改善衰老小鼠的心脏舒张功能。这些发现为EGCG治疗的组蛋白乙酰化机制提供了新的见解，可能有助于预防老年人群中的CDD。
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.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
3.9
作者：
Lambert JD;Elias RJ
通讯作者：
Elias RJ
影响因子：
5
作者：
Ferguson, Bradley S.;McKinsey, Timothy A.
通讯作者：
McKinsey, Timothy A.
影响因子：
--
作者：
Di Lisi R;Picard A;Ausoni S;Schiaffino S
通讯作者：
Schiaffino S
DOI：
10.1016/0735-1097(94)90667-x
发表时间：
1994-06-01
影响因子：
24
作者：
GIANNUZZI, P;IMPARATO, A;GIORDANO, A
通讯作者：
GIORDANO, A