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

BackgroundThe 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...

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Main 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
Format: Article
Language:English
Published: Wiley 2016-04-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.115.002648
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author 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
author_facet 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
author_sort Yuhua Fan
collection DOAJ
description BackgroundThe 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 ResultsWe 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. ConclusionsWe 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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spelling doaj.art-e10ebc95692a408c98d0e30d2a291c2e2022-12-21T23:53:09ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-04-015410.1161/JAHA.115.002648Resveratrol Ameliorates Cardiac Hypertrophy by Down‐regulation of miR‐155 Through Activation of Breast Cancer Type 1 Susceptibility ProteinYuhua Fan0Li Liu1Kun Fang2Tao Huang3Lin Wan4Youbin Liu5Sen Zhang6Dongxia Yan7Guangnan Li8Yanhui Gao9Yanjie Lv10Yanjun Chen11Yingfeng Tu12College of Pharmacy, Harbin Medical University‐Daqing, Daqing, ChinaDepartment of Anesthesiology, The Third Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaCollege of Pharmacy, Harbin Medical University‐Daqing, Daqing, ChinaRadiology Department and Molecular Imaging Center, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaRadiology Department and Molecular Imaging Center, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Cardiology, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, ChinaDepartment of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, ChinaDepartment of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, ChinaDepartment of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, ChinaKey Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, ChinaDepartment of Cardiology, The Fourth Hospital of Harbin Medical University, Nangang District Harbin, Heilongjiang, ChinaBackgroundThe 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 ResultsWe 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. ConclusionsWe 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.https://www.ahajournals.org/doi/10.1161/JAHA.115.002648BRCA1FoxO3amiR‐155resveratrol
spellingShingle 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
Resveratrol Ameliorates Cardiac Hypertrophy by Down‐regulation of miR‐155 Through Activation of Breast Cancer Type 1 Susceptibility Protein
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
BRCA1
FoxO3a
miR‐155
resveratrol
title Resveratrol Ameliorates Cardiac Hypertrophy by Down‐regulation of miR‐155 Through Activation of Breast Cancer Type 1 Susceptibility Protein
title_full Resveratrol Ameliorates Cardiac Hypertrophy by Down‐regulation of miR‐155 Through Activation of Breast Cancer Type 1 Susceptibility Protein
title_fullStr Resveratrol Ameliorates Cardiac Hypertrophy by Down‐regulation of miR‐155 Through Activation of Breast Cancer Type 1 Susceptibility Protein
title_full_unstemmed Resveratrol Ameliorates Cardiac Hypertrophy by Down‐regulation of miR‐155 Through Activation of Breast Cancer Type 1 Susceptibility Protein
title_short Resveratrol Ameliorates Cardiac Hypertrophy by Down‐regulation of miR‐155 Through Activation of Breast Cancer Type 1 Susceptibility Protein
title_sort resveratrol ameliorates cardiac hypertrophy by down regulation of mir 155 through activation of breast cancer type 1 susceptibility protein
topic BRCA1
FoxO3a
miR‐155
resveratrol
url https://www.ahajournals.org/doi/10.1161/JAHA.115.002648
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