Resveratrol Ameliorates Cardiac Hypertrophy by Down-regulation of miR-155 Through Activation of Breast Cancer Type 1 Susceptibility Protein.

Abstract

BACKGROUND:

The polyphenol resveratrol (Rev) has been reported to exhibit cardioprotective effects, such as inhibition of TAC (transverse aortic constriction) or isoprenaline (ISO)-induced hypertrophy. MicroRNA-155 (miR-155) was found to be decreased in hypertrophic myocardium, which could be further reduced by pretreatment of Rev. The study was designed to investigate the molecular effects of miR-155 on cardiac hypertrophy, focusing on the role of breast cancer type 1 susceptibility protein (BRCA1).

METHODS AND RESULTS:

We demonstrated that Rev alleviated severity of hypertrophic myocardium in a mice model of cardiac hypertrophy by TAC treatment. Down-regulation of miR-155 was observed in pressure overload- or ISO-induced hypertrophic cardiomyoctyes. Interestingly, administration of Rev substantially attenuated miR-155 level in cardiomyocytes. In agreement with its miR-155 reducing effect, Rev relieved cardiac hypertrophy and restored cardiac function by activation of BRCA1 in cardiomyoctyes. Our results further revealed that forkhead box O3a (FoxO3a) was a miR-155 target in the heart. And miR-155 directly repressed FoxO3a, whose expression was mitigated in miR-155 agomir and mimic treatment in vivo and in vitro.

CONCLUSIONS:

We conclude that BRCA1 inactivation can increase expression of miR-155, contributing to cardiac hypertrophy. And Rev produces their beneficial effects partially by down-regulating miR-155 expression, which might be a novel strategy for treatment of cardiac hypertrophy.

• Authors: Yuhua Fan, Li Liu, Kun Fang, Tao Huang, Lin Wan, Youbin Liu, Sen Zhang, Dongxia Yan, Guangnan Li, Yanhui Gao, Yanjie Lv, Yanjun Chen, Yingfeng Tu
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 5 Issue 4 (04 22 2016) ISSN: 2047-9980 [Electronic] England
• PMID: 27107135 (Publication Type: Journal Article)
• Copyright: © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Chemical References

• BRCA1 Protein
• Enzyme Inhibitors
• MicroRNAs
• Mirn155 microRNA, mouse
• Stilbenes
• RNA
• Resveratrol

Topics

• Animals
• BRCA1 Protein (genetics, metabolism)
• Blotting, Western
• Cardiomegaly (drug therapy, genetics, metabolism)
• Cells, Cultured
• Disease Models, Animal
• Down-Regulation
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation
• Immunohistochemistry
• Male
• Mice
• MicroRNAs (biosynthesis, genetics)
• Myocytes, Cardiac (metabolism, pathology)
• RNA (genetics)
• Resveratrol
• Reverse Transcriptase Polymerase Chain Reaction
• Stilbenes (pharmacology)