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Original article
Submitted: 2023-05-11
Accepted: 2023-06-03
Published online: 2023-07-05
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Indole-3-propionic acid, a product of intestinal flora, inhibits the HDAC6/NOX2 signaling and relieves doxorubicin-induced cardiomyocyte damage

Chunyan Li1, Jingling Chang2, Yueqi Wang3, Guozhong Pan1
Affiliations
  1. Department of Cardiology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
  2. Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
  3. Department of Traditional Chinese Medicine, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing, China

open access

Ahead of Print
ORIGINAL ARTICLES
Submitted: 2023-05-11
Accepted: 2023-06-03
Published online: 2023-07-05

Abstract

The heart failure-gut hypothesis indicates that damage to intestinal mucosa leads to increased microbial translocation, resulting in alterations in metabolites entering the blood circulation. This process promotes the development of heart failure. This study aimed to reveal the involvement of indole-3-propionic acid (IPA), a microbiota-derived tryptophan metabolite, in heart failure. Human cardiomyocytes AC16 was treated with doxorubicin to induce in vitro heart failure model, the influences of IPA on the cellular viability, apoptosis, inflammation and oxidative stress were evaluated. Molecular docking and western blotting were used to initially illustrate the potential relationship between IPA and HDAC6. Through HDAC6 overexpression, its mediating role in the regulatory mechanism of IPA in the above aspects was further investigated. IPA was found to reduce the apoptosis, inflammation and oxidative stress in doxorubicin-treated cells. The visualized structure displayed that IPA bound to HDAC6 and that IPA reduced HDAC6 level. Additionally, HDAC6 overexpression reversed the regulation of IPA in the above aspects, indicating the HDAC6/NOX2 signals mediated the mechanism of IPA. Together, the present study revealed that IPA reduced oxidative stress, inflammatory response and apoptosis in cardiomyocytes via inhibiting the HDAC6/NOX2 signaling. The findings suggest that gut microbiota metabolites have potential in the treatment of heart failure.

Abstract

The heart failure-gut hypothesis indicates that damage to intestinal mucosa leads to increased microbial translocation, resulting in alterations in metabolites entering the blood circulation. This process promotes the development of heart failure. This study aimed to reveal the involvement of indole-3-propionic acid (IPA), a microbiota-derived tryptophan metabolite, in heart failure. Human cardiomyocytes AC16 was treated with doxorubicin to induce in vitro heart failure model, the influences of IPA on the cellular viability, apoptosis, inflammation and oxidative stress were evaluated. Molecular docking and western blotting were used to initially illustrate the potential relationship between IPA and HDAC6. Through HDAC6 overexpression, its mediating role in the regulatory mechanism of IPA in the above aspects was further investigated. IPA was found to reduce the apoptosis, inflammation and oxidative stress in doxorubicin-treated cells. The visualized structure displayed that IPA bound to HDAC6 and that IPA reduced HDAC6 level. Additionally, HDAC6 overexpression reversed the regulation of IPA in the above aspects, indicating the HDAC6/NOX2 signals mediated the mechanism of IPA. Together, the present study revealed that IPA reduced oxidative stress, inflammatory response and apoptosis in cardiomyocytes via inhibiting the HDAC6/NOX2 signaling. The findings suggest that gut microbiota metabolites have potential in the treatment of heart failure.

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Keywords

gut microbiome metabolites, heart failure, doxorubicin, IPA, oxidative stress

About this article
Title

Indole-3-propionic acid, a product of intestinal flora, inhibits the HDAC6/NOX2 signaling and relieves doxorubicin-induced cardiomyocyte damage

Journal

Folia Morphologica

Issue

Ahead of Print

Article type

Original article

Published online

2023-07-05

Page views

518

Article views/downloads

539

DOI

10.5603/FM.a2023.0046

Pubmed

37431150

Keywords

gut microbiome metabolites
heart failure
doxorubicin
IPA
oxidative stress

Authors

Chunyan Li
Jingling Chang
Yueqi Wang
Guozhong Pan

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