Suberoylanilide Hydroxamic Acid Improves Cardiac Hypertrophy via Inhibiting Histone Deacetylase in Experimental Mice
10.3969/j.issn.1000-3614.2017.08.017
- VernacularTitle:辛二酰苯胺异羟肟酸通过抑制组蛋白去乙酰化酶改善小鼠心肌肥厚的研究
- Author:
Chang PENG
;
Shuo LI
;
Xiaomei LUO
;
Xinxing XIE
;
Mingchen XIAO
- Keywords:
Histone deacetylasel l;
Cardiomegaly;
Treatment Outcome
- From:
Chinese Circulation Journal
2017;32(8):803-807
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the effect of suberoylanilide hydroxamic acid (SAHA) improving cardiac hypertrophy via inhibiting histone deacetylases (HDAC) in experimental mice and to provide a new idea for prevention and treatment of cardiac hypertrophy. Methods: Cardiac hypertrophy mice model was established by thoracic aorta ligation. A total of 60 Kunming mice were randomly divided into 4 groups: Normal control group, Sham operation group, Cardiac hypertrophy (CH) group and CH+SAHA group. There were 6 mice used in each group. Myocardial cell morphology was observed by HE staining, cardiac function was assessed by echocardiography, mRNA and protein expressions of HDAC5 (the isoform of HDAC) and β-MHC were examined by RT-PCR and Western blot analysis. Results: The mice in CH group had myocardial cell hypertrophy, disordered arrangement and hyperchromatic nucleus. Compared with Sham operation group, CH group showed decreased left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic volume (LVEDV) and increased thickness of inter-ventricular septum (IVS), allP<0.05; CH group presented elevated mRNA and protein expressions of HDAC5 and β-MHC,P<0.05. SAHA obviously decreased HDAC5 expression, down regulated cardiac hypertrophy related β-MHC gene expression, improved cardiac function and hypertrophy, all P<0.05. Conclusion: HDAC were involved in myocardial hypertrophy; SAHA could inhibit HDAC expression and therefore,improved myocardial hypertrophy in experimental mice.