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



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.



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.
College of Pharmacy, Harbin Medical University-Daqing, Daqing, China.
Yuhua
Y
Fan
Department of Anesthesiology, The Third Hospital of Harbin Medical University, Harbin, Heilongjiang, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
Li
L
Liu
College of Pharmacy, Harbin Medical University-Daqing, Daqing, China.
Kun
K
Fang
Radiology Department and Molecular Imaging Center, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Tao
T
Huang
Radiology Department and Molecular Imaging Center, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Lin
L
Wan
Department of Cardiology, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Youbin
Y
Liu
Department of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, China.
Sen
S
Zhang
Department of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, China.
Dongxia
D
Yan
Department of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, China.
Guangnan
G
Li
Department of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, China.
Yanhui
Y
Gao
Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China College of Pharmacy, Harbin Medical University, Harbin, China.
Yanjie
Y
Lv
Department of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, China tyfdoctor@163.com yanjunchen@163.com.
Yanjun
Y
Chen
Department of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China tyfdoctor@163.com yanjunchen@163.com.
Yingfeng
Y
Tu
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D006332:Cardiomegaly / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000235:genetics; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*
D019313:BRCA1 Protein; D004791:Enzyme Inhibitors; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D013267:Stilbenes; D012313:RNA; D000077185:Resveratrol
BRCA1; FoxO3a; miR‐155; resveratrol