期刊
JOURNAL OF THE AMERICAN HEART ASSOCIATION
卷 5, 期 4, 页码 -出版社
WILEY-BLACKWELL
DOI: 10.1161/JAHA.115.002648
关键词
BRCA1; FoxO3a; miR-155; resveratrol
资金
- National Natural Science Foundation of China [81401457, 81503069, 81400204, 81301255]
- Harbin Medical University [DQ2014-03]
- China Postdoctoral Science Foundation [2015M571449, 2015M581490, 2014M561376]
- Heilongjiang Health and Family Planning Commission [2014-385]
- Postdoctoral Science Foundation of Heilongjiang Province [LBH-Z14143]
- Natural Science Foundation of Heilongjiang Province [D201101]
- Natural Science Foundation of Heilongjiang Province of China for Returnees [LC2015038]
- Harbin Municipal Science and Technology Research Fund [2013RFLYJ012]
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.
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