Role of histone acetylation modification imbalance in regulation of cardiac hypertrophy induced by phenylephrine
10.3969/j.issn.1000-4718.2017.02.006
- VernacularTitle:组蛋白乙酰化修饰失衡在苯肾上腺素诱导小鼠心肌肥厚中的调控作用
- Author:
Chang PENG
;
Xiaomei LUO
;
Shuo LI
;
Huichao SUN
- Keywords:
Phenylephrine;
Cardiac hypertrophy;
Hyperacetylation
- From:
Chinese Journal of Pathophysiology
2017;33(2):227-232
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM: To investigate the regulatory mechanism of histone acetylation on cardiac hypertrophy in -duced by phenylephrine , and to provide a new idea for preventing and curing hypertrophic cardiomyopathy .METHODS:Phenylephrine was given by continuous subcutaneous injection for modeling cardiac hypertrophy in C 57BL/6 mice.The le-vel of histone H3 lysine 27 acetylation (H3K27ac) in the promoter of cardiac nuclear transcription factor GATA4 and the mRNA expression of GATA4 were identified by chromatin immunoprecipitation (ChIP) and real-time PCR, respectively. Meanwhile, the protein expression of histone H3K27ac, atrial natriuretic peptide (ANP) and α-myosin heavy chain (α-MHC) was determined by Western blot .Cardiac hypertrophy in the mice was observed by HE staining and echocardio-graphy.RESULTS:The results of Western blot showed that the level of histone H 3K27ac in phenylephrine group was sig-nificantly increased compared with normal saline group (P<0.05), and ChIP-qPCR data showed that the level of histone H3K27ac in the promoter of GATA4 was increased significantly in the same samples (P<0.05).The expression levels of GATA4 mRNA and ANP protein in phenylephrine group were apparently increased compared with normal saline group ( P<0.05).However, histone acetylase inhibitor anacardic acid attenuated histone H 3K27 hyperacetylation induced by pheny-lephrine, and downregulated the over-expression of GATA4 and ANP in the heart of the mice (P<0.05).HE staining and echocardiography data showed that phenylephrine apparently increased left ventricular posterior wall thickness and de -creased left ventricular end-systolic diameter and left ventricular end-diastolic diameter , while anacardic acid also reversed these indexes that mentioned above and attenuated cardiac hypertrophy induced by phenylephrine in the mice .CONCLU-SION:Histone acetylation modification imbalance is involved in cardiac hypertrophy induced by phenylephrine , and the histone acetylase inhibitor anacardic acid decreases histone hyperacetylation induced by phenylephrine and attenuates car -diac hypertrophy in the mice .
