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Chronic Kidney Disease Increases Atrial Fibrillation Inducibility: Involvement of Inflammation, Atrial Fibrosis, and Connexins

Chronic kidney disease (CKD) causes atrial structural remodeling and subsequently increases the incidence of atrial fibrillation (AF). Atrial connexins and inflammatory responses may be involved in this remodeling process. In this study, nephrectomy was used to produce the CKD rat model. Three month...

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Autores principales: Qiu, Huiliang, Ji, Chunlan, Liu, Wei, Wu, Yuchi, Lu, Zhaoyu, Lin, Qizhan, Xue, Zheng, Liu, Xusheng, Wu, Huanlin, Jiang, Wei, Zou, Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288485/
https://www.ncbi.nlm.nih.gov/pubmed/30564139
http://dx.doi.org/10.3389/fphys.2018.01726
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author Qiu, Huiliang
Ji, Chunlan
Liu, Wei
Wu, Yuchi
Lu, Zhaoyu
Lin, Qizhan
Xue, Zheng
Liu, Xusheng
Wu, Huanlin
Jiang, Wei
Zou, Chuan
author_facet Qiu, Huiliang
Ji, Chunlan
Liu, Wei
Wu, Yuchi
Lu, Zhaoyu
Lin, Qizhan
Xue, Zheng
Liu, Xusheng
Wu, Huanlin
Jiang, Wei
Zou, Chuan
author_sort Qiu, Huiliang
collection PubMed
description Chronic kidney disease (CKD) causes atrial structural remodeling and subsequently increases the incidence of atrial fibrillation (AF). Atrial connexins and inflammatory responses may be involved in this remodeling process. In this study, nephrectomy was used to produce the CKD rat model. Three months post-nephrectomy, cardiac structure, function and AF vulnerability were quantified using echocardiography and electrophysiology methods. The left atrial tissue was tested for quantification of fibrosis and inflammation, and for the distribution and expression of connexin (Cx) 40 and Cx43. An echocardiography showed that CKD resulted in the left atrial enlargement and left ventricular hypertrophy, but had no functional changes. CKD caused a significant increase in the AF inducible rate (91.11% in CKD group vs. 6.67% in sham group, P < 0.001) and the AF duration [107 (0–770) s in CKD vs. 0 (0–70) s in sham, P < 0.001] with prolonged P-wave duration. CKD induced severe interstitial fibrosis, activated the transforming growth factor-β1/Smad2/3 pathway with a massive extracellular matrix deposition of collagen type I and α-smooth muscle actin, and matured the NLR (nucleotide-binding domain leucine-rich repeat-containing receptor) pyrin domain-containing protein 3 (NLRP3) inflammasome with an inflammatory cascade response. CKD resulted in an increase in non-phosphorylated-Cx43, a decrease in Cx40 and phosphorylated-Cx43, and lateralized the distribution of Cx40 and Cx43 proteins with upregulations of Rac-1, connective tissue growth factor and N-cadherin. These findings implicate the transforming growth factor-β1/Smad2/3, the NLRP3 inflammasome and the connexins as potential mediators of increased AF vulnerability in CKD.
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spelling pubmed-62884852018-12-18 Chronic Kidney Disease Increases Atrial Fibrillation Inducibility: Involvement of Inflammation, Atrial Fibrosis, and Connexins Qiu, Huiliang Ji, Chunlan Liu, Wei Wu, Yuchi Lu, Zhaoyu Lin, Qizhan Xue, Zheng Liu, Xusheng Wu, Huanlin Jiang, Wei Zou, Chuan Front Physiol Physiology Chronic kidney disease (CKD) causes atrial structural remodeling and subsequently increases the incidence of atrial fibrillation (AF). Atrial connexins and inflammatory responses may be involved in this remodeling process. In this study, nephrectomy was used to produce the CKD rat model. Three months post-nephrectomy, cardiac structure, function and AF vulnerability were quantified using echocardiography and electrophysiology methods. The left atrial tissue was tested for quantification of fibrosis and inflammation, and for the distribution and expression of connexin (Cx) 40 and Cx43. An echocardiography showed that CKD resulted in the left atrial enlargement and left ventricular hypertrophy, but had no functional changes. CKD caused a significant increase in the AF inducible rate (91.11% in CKD group vs. 6.67% in sham group, P < 0.001) and the AF duration [107 (0–770) s in CKD vs. 0 (0–70) s in sham, P < 0.001] with prolonged P-wave duration. CKD induced severe interstitial fibrosis, activated the transforming growth factor-β1/Smad2/3 pathway with a massive extracellular matrix deposition of collagen type I and α-smooth muscle actin, and matured the NLR (nucleotide-binding domain leucine-rich repeat-containing receptor) pyrin domain-containing protein 3 (NLRP3) inflammasome with an inflammatory cascade response. CKD resulted in an increase in non-phosphorylated-Cx43, a decrease in Cx40 and phosphorylated-Cx43, and lateralized the distribution of Cx40 and Cx43 proteins with upregulations of Rac-1, connective tissue growth factor and N-cadherin. These findings implicate the transforming growth factor-β1/Smad2/3, the NLRP3 inflammasome and the connexins as potential mediators of increased AF vulnerability in CKD. Frontiers Media S.A. 2018-12-04 /pmc/articles/PMC6288485/ /pubmed/30564139 http://dx.doi.org/10.3389/fphys.2018.01726 Text en Copyright © 2018 Qiu, Ji, Liu, Wu, Lu, Lin, Xue, Liu, Wu, Jiang and Zou. 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 Physiology
Qiu, Huiliang
Ji, Chunlan
Liu, Wei
Wu, Yuchi
Lu, Zhaoyu
Lin, Qizhan
Xue, Zheng
Liu, Xusheng
Wu, Huanlin
Jiang, Wei
Zou, Chuan
Chronic Kidney Disease Increases Atrial Fibrillation Inducibility: Involvement of Inflammation, Atrial Fibrosis, and Connexins
title Chronic Kidney Disease Increases Atrial Fibrillation Inducibility: Involvement of Inflammation, Atrial Fibrosis, and Connexins
title_full Chronic Kidney Disease Increases Atrial Fibrillation Inducibility: Involvement of Inflammation, Atrial Fibrosis, and Connexins
title_fullStr Chronic Kidney Disease Increases Atrial Fibrillation Inducibility: Involvement of Inflammation, Atrial Fibrosis, and Connexins
title_full_unstemmed Chronic Kidney Disease Increases Atrial Fibrillation Inducibility: Involvement of Inflammation, Atrial Fibrosis, and Connexins
title_short Chronic Kidney Disease Increases Atrial Fibrillation Inducibility: Involvement of Inflammation, Atrial Fibrosis, and Connexins
title_sort chronic kidney disease increases atrial fibrillation inducibility: involvement of inflammation, atrial fibrosis, and connexins
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288485/
https://www.ncbi.nlm.nih.gov/pubmed/30564139
http://dx.doi.org/10.3389/fphys.2018.01726
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