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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Frontiers Media S.A.
2020-11-01
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Series: | Frontiers in Cardiovascular Medicine |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2020.582890/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yan Wang Yan Wang Yan Wang Yan Wang Zengshuo Xie Zengshuo Xie Zengshuo Xie Nan Jiang Zexuan Wu Zexuan Wu Ruicong Xue Ruicong Xue Bin Dong Bin Dong Wendong Fan Wendong Fan Gang Dai Gang Dai Chen Chen Chen Chen Jiayong Li Jiayong Li Hao Chen Hao Chen Zi Ye Rong Fang Rong Fang Manting Choy Manting Choy Jingjing Zhao Jingjing Zhao Yugang Dong Yugang Dong Yugang Dong Chen Liu Chen Liu Chen Liu |
spellingShingle |
Yan Wang Yan Wang Yan Wang Yan Wang Zengshuo Xie Zengshuo Xie Zengshuo Xie Nan Jiang Zexuan Wu Zexuan Wu Ruicong Xue Ruicong Xue Bin Dong Bin Dong Wendong Fan Wendong Fan Gang Dai Gang Dai Chen Chen Chen Chen Jiayong Li Jiayong Li Hao Chen Hao Chen Zi Ye Rong Fang Rong Fang Manting Choy Manting Choy Jingjing Zhao Jingjing Zhao Yugang Dong Yugang Dong Yugang Dong Chen Liu Chen Liu Chen Liu Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction Frontiers in Cardiovascular Medicine cardiac hypertrophy hispidulin mitochondrial dysfunction heart failure oxidative stress |
author_facet |
Yan Wang Yan Wang Yan Wang Yan Wang Zengshuo Xie Zengshuo Xie Zengshuo Xie Nan Jiang Zexuan Wu Zexuan Wu Ruicong Xue Ruicong Xue Bin Dong Bin Dong Wendong Fan Wendong Fan Gang Dai Gang Dai Chen Chen Chen Chen Jiayong Li Jiayong Li Hao Chen Hao Chen Zi Ye Rong Fang Rong Fang Manting Choy Manting Choy Jingjing Zhao Jingjing Zhao Yugang Dong Yugang Dong Yugang Dong Chen Liu Chen Liu Chen Liu |
author_sort |
Yan Wang |
title |
Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction |
title_short |
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_sort |
hispidulin attenuates cardiac hypertrophy by improving mitochondrial dysfunction |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cardiovascular Medicine |
issn |
2297-055X |
publishDate |
2020-11-01 |
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. |
topic |
cardiac hypertrophy hispidulin mitochondrial dysfunction heart failure oxidative stress |
url |
https://www.frontiersin.org/articles/10.3389/fcvm.2020.582890/full |
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doaj-01b2e368740046eebaa0da1eab2a1a652020-12-08T08:42:53ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2020-11-01710.3389/fcvm.2020.582890582890Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial DysfunctionYan Wang0Yan Wang1Yan Wang2Yan Wang3Zengshuo Xie4Zengshuo Xie5Zengshuo Xie6Nan Jiang7Zexuan Wu8Zexuan Wu9Ruicong Xue10Ruicong Xue11Bin Dong12Bin Dong13Wendong Fan14Wendong Fan15Gang Dai16Gang Dai17Chen Chen18Chen Chen19Jiayong Li20Jiayong Li21Hao Chen22Hao Chen23Zi Ye24Rong Fang25Rong Fang26Manting Choy27Manting Choy28Jingjing Zhao29Jingjing Zhao30Yugang Dong31Yugang Dong32Yugang Dong33Chen Liu34Chen Liu35Chen Liu36Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiology, The Second People's Hospital of Guangdong Province, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaFaculty of Medicine, St Vincent Clinical School, University of New South Wales, Sydney, NSW, AustraliaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaNHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, ChinaCardiac 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.https://www.frontiersin.org/articles/10.3389/fcvm.2020.582890/fullcardiac hypertrophyhispidulinmitochondrial dysfunctionheart failureoxidative stress |