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Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice

Atrial fibrosis and atrial inflammation are associated with the pathogenesis of atrial fibrillation (AF). Basic helix–loop–helix family member E40 (Bhlhe40) is an important transcription factor, which is involved in tumors, inflammation, apoptosis, viral infection, and hypoxia. However, its role and...

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Autores principales: Ren, Kai-Wen, Yu, Xiao-Hong, Gu, Yu-Hui, Xie, Xin, Wang, Yu, Wang, Shi-hao, Li, Hui-Hua, Bi, Hai-Lian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592817/
https://www.ncbi.nlm.nih.gov/pubmed/36304536
http://dx.doi.org/10.3389/fcvm.2022.957903
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author Ren, Kai-Wen
Yu, Xiao-Hong
Gu, Yu-Hui
Xie, Xin
Wang, Yu
Wang, Shi-hao
Li, Hui-Hua
Bi, Hai-Lian
author_facet Ren, Kai-Wen
Yu, Xiao-Hong
Gu, Yu-Hui
Xie, Xin
Wang, Yu
Wang, Shi-hao
Li, Hui-Hua
Bi, Hai-Lian
author_sort Ren, Kai-Wen
collection PubMed
description Atrial fibrosis and atrial inflammation are associated with the pathogenesis of atrial fibrillation (AF). Basic helix–loop–helix family member E40 (Bhlhe40) is an important transcription factor, which is involved in tumors, inflammation, apoptosis, viral infection, and hypoxia. However, its role and molecular mechanism in AF remain unclear. In this study, a mouse model of AF was induced by Ang II infusion. The atrial diameter was evaluated using echocardiography. Induction and duration of AF were measured by programmed electrical stimulation. Atrial structural remodeling was detected using routine histologic examinations. Our results showed that Bhlhe40 was significantly upregulated in angiotensin II (Ang II)-stimulated atrial cardiomyocytes and atrial tissues and in tissues from patients with AF. Cardiac-specific knockdown of Bhlhe40 in mice by a type 9 recombinant adeno-associated virus (rAAV9)-shBhlhe40 significantly ameliorated Ang II-induced atrial dilatation, atrial fibrosis, and atrial inflammation, as well as the inducibility and duration of AF. Mechanistically, cardiac-specific knockdown of Bhlhe40 attenuated Ang II-induced activation of NF-κB/NLRP3, TGF-1β/Smad2 signals, the increased expression of CX43, and the decreased expression of Kv4.3 in the atria. This is the first study to suggest that Bhlhe40 is a novel regulator of AF progression, and identifying Bhlhe40 may be a new therapeutic target for hypertrophic remodeling and heart failure.
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spelling pubmed-95928172022-10-26 Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice Ren, Kai-Wen Yu, Xiao-Hong Gu, Yu-Hui Xie, Xin Wang, Yu Wang, Shi-hao Li, Hui-Hua Bi, Hai-Lian Front Cardiovasc Med Cardiovascular Medicine Atrial fibrosis and atrial inflammation are associated with the pathogenesis of atrial fibrillation (AF). Basic helix–loop–helix family member E40 (Bhlhe40) is an important transcription factor, which is involved in tumors, inflammation, apoptosis, viral infection, and hypoxia. However, its role and molecular mechanism in AF remain unclear. In this study, a mouse model of AF was induced by Ang II infusion. The atrial diameter was evaluated using echocardiography. Induction and duration of AF were measured by programmed electrical stimulation. Atrial structural remodeling was detected using routine histologic examinations. Our results showed that Bhlhe40 was significantly upregulated in angiotensin II (Ang II)-stimulated atrial cardiomyocytes and atrial tissues and in tissues from patients with AF. Cardiac-specific knockdown of Bhlhe40 in mice by a type 9 recombinant adeno-associated virus (rAAV9)-shBhlhe40 significantly ameliorated Ang II-induced atrial dilatation, atrial fibrosis, and atrial inflammation, as well as the inducibility and duration of AF. Mechanistically, cardiac-specific knockdown of Bhlhe40 attenuated Ang II-induced activation of NF-κB/NLRP3, TGF-1β/Smad2 signals, the increased expression of CX43, and the decreased expression of Kv4.3 in the atria. This is the first study to suggest that Bhlhe40 is a novel regulator of AF progression, and identifying Bhlhe40 may be a new therapeutic target for hypertrophic remodeling and heart failure. Frontiers Media S.A. 2022-10-11 /pmc/articles/PMC9592817/ /pubmed/36304536 http://dx.doi.org/10.3389/fcvm.2022.957903 Text en Copyright © 2022 Ren, Yu, Gu, Xie, Wang, Wang, Li and Bi. 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 Cardiovascular Medicine
Ren, Kai-Wen
Yu, Xiao-Hong
Gu, Yu-Hui
Xie, Xin
Wang, Yu
Wang, Shi-hao
Li, Hui-Hua
Bi, Hai-Lian
Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice
title Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice
title_full Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice
title_fullStr Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice
title_full_unstemmed Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice
title_short Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice
title_sort cardiac-specific knockdown of bhlhe40 attenuates angiotensin ii (ang ii)-induced atrial fibrillation in mice
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592817/
https://www.ncbi.nlm.nih.gov/pubmed/36304536
http://dx.doi.org/10.3389/fcvm.2022.957903
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