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Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway
Cardiac hypertrophy is an important characteristic in the development of hypertensive heart disease. Mitochondrial dysfunction plays an important role in the pathology of cardiac hypertrophy. Recent studies have shown that sirtuin 3 (SIRT3)/poly (ADP-ribose) polymerase-1 (PARP-1) pathway modulation...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581039/ https://www.ncbi.nlm.nih.gov/pubmed/34776960 http://dx.doi.org/10.3389/fphar.2021.739615 |
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author | Chen, Wen-Jing Cheng, Yan Li, Wen Dong, Xiao-Kang Wei, Jian-liang Yang, Chuan-Hua Jiang, Yue-Hua |
author_facet | Chen, Wen-Jing Cheng, Yan Li, Wen Dong, Xiao-Kang Wei, Jian-liang Yang, Chuan-Hua Jiang, Yue-Hua |
author_sort | Chen, Wen-Jing |
collection | PubMed |
description | Cardiac hypertrophy is an important characteristic in the development of hypertensive heart disease. Mitochondrial dysfunction plays an important role in the pathology of cardiac hypertrophy. Recent studies have shown that sirtuin 3 (SIRT3)/poly (ADP-ribose) polymerase-1 (PARP-1) pathway modulation inhibits cardiac hypertrophy. Quercetin, a natural flavonol agent, has been reported to attenuate cardiac hypertrophy. However, the molecular mechanism is not completely elucidated. In this study, we aimed to explore the mechanism underlying the protective effect of quercetin on cardiac hypertrophy. Spontaneously hypertensive rats (SHRs) were treated with quercetin (20 mg/kg/d) for 8 weeks to evaluate the effects of quercetin on blood pressure and cardiac hypertrophy. Additionally, the mitochondrial protective effect of quercetin was assessed in H9c2 cells treated with Ang II. SHRs displayed aggravated cardiac hypertrophy and fibrosis, which were attenuated by quercetin treatment. Quercetin also improved cardiac function, reduced mitochondrial superoxide and protected mitochondrial structure in vivo. In vitro, Ang II increased the mRNA level of hypertrophic markers including atrial natriuretic factor (ANF) and β-myosin heavy chain (β-MHC), whereas quercetin ameliorated this hypertrophic response. Moreover, quercetin prevented mitochondrial function against Ang II induction. Importantly, mitochondrial protection and PARP-1 inhibition by quercetin were partly abolished after SIRT3 knockdown. Our results suggested that quercetin protected mitochondrial function by modulating SIRT3/PARP-1 pathway, contributing to the inhibition of cardiac hypertrophy. |
format | Online Article Text |
id | pubmed-8581039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85810392021-11-12 Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway Chen, Wen-Jing Cheng, Yan Li, Wen Dong, Xiao-Kang Wei, Jian-liang Yang, Chuan-Hua Jiang, Yue-Hua Front Pharmacol Pharmacology Cardiac hypertrophy is an important characteristic in the development of hypertensive heart disease. Mitochondrial dysfunction plays an important role in the pathology of cardiac hypertrophy. Recent studies have shown that sirtuin 3 (SIRT3)/poly (ADP-ribose) polymerase-1 (PARP-1) pathway modulation inhibits cardiac hypertrophy. Quercetin, a natural flavonol agent, has been reported to attenuate cardiac hypertrophy. However, the molecular mechanism is not completely elucidated. In this study, we aimed to explore the mechanism underlying the protective effect of quercetin on cardiac hypertrophy. Spontaneously hypertensive rats (SHRs) were treated with quercetin (20 mg/kg/d) for 8 weeks to evaluate the effects of quercetin on blood pressure and cardiac hypertrophy. Additionally, the mitochondrial protective effect of quercetin was assessed in H9c2 cells treated with Ang II. SHRs displayed aggravated cardiac hypertrophy and fibrosis, which were attenuated by quercetin treatment. Quercetin also improved cardiac function, reduced mitochondrial superoxide and protected mitochondrial structure in vivo. In vitro, Ang II increased the mRNA level of hypertrophic markers including atrial natriuretic factor (ANF) and β-myosin heavy chain (β-MHC), whereas quercetin ameliorated this hypertrophic response. Moreover, quercetin prevented mitochondrial function against Ang II induction. Importantly, mitochondrial protection and PARP-1 inhibition by quercetin were partly abolished after SIRT3 knockdown. Our results suggested that quercetin protected mitochondrial function by modulating SIRT3/PARP-1 pathway, contributing to the inhibition of cardiac hypertrophy. Frontiers Media S.A. 2021-10-28 /pmc/articles/PMC8581039/ /pubmed/34776960 http://dx.doi.org/10.3389/fphar.2021.739615 Text en Copyright © 2021 Chen, Cheng, Li, Dong, Wei, Yang and Jiang. https://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 | Pharmacology Chen, Wen-Jing Cheng, Yan Li, Wen Dong, Xiao-Kang Wei, Jian-liang Yang, Chuan-Hua Jiang, Yue-Hua Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway |
title | Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway |
title_full | Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway |
title_fullStr | Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway |
title_full_unstemmed | Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway |
title_short | Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway |
title_sort | quercetin attenuates cardiac hypertrophy by inhibiting mitochondrial dysfunction through sirt3/parp-1 pathway |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581039/ https://www.ncbi.nlm.nih.gov/pubmed/34776960 http://dx.doi.org/10.3389/fphar.2021.739615 |
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