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Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction

Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development...

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Autores principales: Wang, Yan, Xie, Zengshuo, Jiang, Nan, Wu, Zexuan, Xue, Ruicong, Dong, Bin, Fan, Wendong, Dai, Gang, Chen, Chen, Li, Jiayong, Chen, Hao, Ye, Zi, Fang, Rong, Choy, Manting, Zhao, Jingjing, Dong, Yugang, Liu, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726192/
https://www.ncbi.nlm.nih.gov/pubmed/33324687
http://dx.doi.org/10.3389/fcvm.2020.582890
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author Wang, Yan
Xie, Zengshuo
Jiang, Nan
Wu, Zexuan
Xue, Ruicong
Dong, Bin
Fan, Wendong
Dai, Gang
Chen, Chen
Li, Jiayong
Chen, Hao
Ye, Zi
Fang, Rong
Choy, Manting
Zhao, Jingjing
Dong, Yugang
Liu, Chen
author_facet Wang, Yan
Xie, Zengshuo
Jiang, Nan
Wu, Zexuan
Xue, Ruicong
Dong, Bin
Fan, Wendong
Dai, Gang
Chen, Chen
Li, Jiayong
Chen, Hao
Ye, Zi
Fang, Rong
Choy, Manting
Zhao, Jingjing
Dong, Yugang
Liu, Chen
author_sort Wang, Yan
collection PubMed
description Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac hypertrophy and its underlying mechanism remains unknown. We found that hispidulin significantly inhibited pressure overload-induced cardiac hypertrophy and improved cardiac function in vivo and blocked phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro. We further proved that hispidulin remarkably improved mitochondrial function, manifested by increased electron transport chain (ETC) subunits expression, elevated ATP production, increased oxygen consumption rates (OCR), normalized mitochondrial morphology, and reduced oxidative stress. Furthermore, we discovered that Sirt1, a well-recognized regulator of mitochondrial function, might be a target of hispidulin, as evidenced by its upregulation after hispidulin treatment. Cotreatment with EX527 (a Sirt1-specific inhibitor) and hispidulin nearly completely abolished the antihypertrophic and protective effects of hispidulin on mitochondrial function, providing further evidence that Sirt1 could be the pivotal downstream effector of hispidulin in regulating cardiac hypertrophy.
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spelling pubmed-77261922020-12-14 Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction Wang, Yan Xie, Zengshuo Jiang, Nan Wu, Zexuan Xue, Ruicong Dong, Bin Fan, Wendong Dai, Gang Chen, Chen Li, Jiayong Chen, Hao Ye, Zi Fang, Rong Choy, Manting Zhao, Jingjing Dong, Yugang Liu, Chen Front Cardiovasc Med Cardiovascular Medicine Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac hypertrophy and its underlying mechanism remains unknown. We found that hispidulin significantly inhibited pressure overload-induced cardiac hypertrophy and improved cardiac function in vivo and blocked phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro. We further proved that hispidulin remarkably improved mitochondrial function, manifested by increased electron transport chain (ETC) subunits expression, elevated ATP production, increased oxygen consumption rates (OCR), normalized mitochondrial morphology, and reduced oxidative stress. Furthermore, we discovered that Sirt1, a well-recognized regulator of mitochondrial function, might be a target of hispidulin, as evidenced by its upregulation after hispidulin treatment. Cotreatment with EX527 (a Sirt1-specific inhibitor) and hispidulin nearly completely abolished the antihypertrophic and protective effects of hispidulin on mitochondrial function, providing further evidence that Sirt1 could be the pivotal downstream effector of hispidulin in regulating cardiac hypertrophy. Frontiers Media S.A. 2020-11-26 /pmc/articles/PMC7726192/ /pubmed/33324687 http://dx.doi.org/10.3389/fcvm.2020.582890 Text en Copyright © 2020 Wang, Xie, Jiang, Wu, Xue, Dong, Fan, Dai, Chen, Li, Chen, Ye, Fang, Choy, Zhao, Dong and Liu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Wang, Yan
Xie, Zengshuo
Jiang, Nan
Wu, Zexuan
Xue, Ruicong
Dong, Bin
Fan, Wendong
Dai, Gang
Chen, Chen
Li, Jiayong
Chen, Hao
Ye, Zi
Fang, Rong
Choy, Manting
Zhao, Jingjing
Dong, Yugang
Liu, Chen
Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction
title Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction
title_full Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction
title_fullStr Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction
title_full_unstemmed Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction
title_short Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction
title_sort hispidulin attenuates cardiac hypertrophy by improving mitochondrial dysfunction
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726192/
https://www.ncbi.nlm.nih.gov/pubmed/33324687
http://dx.doi.org/10.3389/fcvm.2020.582890
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