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Cardiovascular Diabetology

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Open Access 01-12-2015 | Original investigation

Histone deacetylase (HDAC) inhibition improves myocardial function and prevents cardiac remodeling in diabetic mice

Authors: Youfang Chen, Jianfeng Du, Yu Tina Zhao, Ling Zhang, Guorong Lv, Shougang Zhuang, Gangjian Qin, Ting C Zhao

Published in: Cardiovascular Diabetology | Issue 1/2015

Abstract

Background

Recent evidence indicates that inhibition of histone deacetylase (HDAC) protects the heart against myocardial injury and stimulates endogenous angiomyogenesis. However, it remains unknown whether HDAC inhibition produces the protective effect in the diabetic heart. We sought to determine whether HDAC inhibition preserves cardiac performance and suppresses cardiac remodeling in diabetic cardiomyopathy.

Methods

Adult ICR mice received an intraperitoneal injection of either streptozotocin (STZ, 200 mg/kg) to establish the diabetic model or vehicle to serve as control. Once hyperglycemia was confirmed, diabetic mice received sodium butyrate (1%), a specific HDAC inhibitor, in drinking water on a daily basis to inhibit HDAC activity. Mice were randomly divided into following groups, which includes Control, Control + Sodium butyrate (NaBu), STZ and STZ + Sodium butyrate (NaBu), respectively. Myocardial function was serially assessed at 7, 14, 21 weeks following treatments.

Results

Echocardiography demonstrated that cardiac function was depressed in diabetic mice, but HDAC inhibition resulted in a significant functional improvement in STZ-injected mice. Likewise, HDAC inhibition attenuates cardiac hypertrophy, as evidenced by a reduced heart/tibia ratio and areas of cardiomyocytes, which is associated with reduced interstitial fibrosis and decreases in active caspase-3 and apoptotic stainings, but also increased angiogenesis in diabetic myocardium. Notably, glucose transporters (GLUT) 1 and 4 were up-regulated following HDAC inhibition, which was accompanied with increases of GLUT1 acetylation and p38 phosphorylation. Furthermore, myocardial superoxide dismutase, an important antioxidant, was elevated following HDAC inhibition in the diabetic mice.

Conclusion

HDAC inhibition plays a critical role in improving cardiac function and suppressing myocardial remodeling in diabetic heart.

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Title: Histone deacetylase (HDAC) inhibition improves myocardial function and prevents cardiac remodeling in diabetic mice
Authors: Youfang Chen
Jianfeng Du
Yu Tina Zhao
Ling Zhang
Guorong Lv
Shougang Zhuang
Gangjian Qin
Ting C Zhao
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/s12933-015-0262-8

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Results

Conclusion

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