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C-type natriuretic peptide prevents angiotensin II-induced atrial connexin 40 and 43 dysregulation by activating AMP-activated kinase signaling

C-type natriuretic peptide (CNP), from the family of natriuretic peptides (NPs), has been shown to induce antihypertrophic and antifibrotic effects in cardiomyocytes. However, the roles of CNP in the atrial dysregulation of connexin (Cx)40 and Cx43 remain to be elucidated. The present study aimed to...

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Autores principales: Ding, Da-Zhi, Jia, Ya-Nan, Zhang, Bo, Guan, Cheng-Ming, Zhou, Shuai, Li, Xiang, Cui, Xun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854524/
https://www.ncbi.nlm.nih.gov/pubmed/31638216
http://dx.doi.org/10.3892/mmr.2019.10744
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author Ding, Da-Zhi
Jia, Ya-Nan
Zhang, Bo
Guan, Cheng-Ming
Zhou, Shuai
Li, Xiang
Cui, Xun
author_facet Ding, Da-Zhi
Jia, Ya-Nan
Zhang, Bo
Guan, Cheng-Ming
Zhou, Shuai
Li, Xiang
Cui, Xun
author_sort Ding, Da-Zhi
collection PubMed
description C-type natriuretic peptide (CNP), from the family of natriuretic peptides (NPs), has been shown to induce antihypertrophic and antifibrotic effects in cardiomyocytes. However, the roles of CNP in the atrial dysregulation of connexin (Cx)40 and Cx43 remain to be elucidated. The present study aimed to investigate the effects of CNP on angiotensin (Ang) II-induced Cx40 and Cx43 dysregulation in isolated perfused beating rat left atria. A rat isolated perfused beating atrial model was used and the protein levels were determined via western blotting. Ang II significantly upregulated NF-κB, activator protein-1, transforming growth factor-β1 (TGF-β1), collagen I and matrix metalloproteinase 2, leading to atrial fibrosis, and downregulated expression of Cx40 and Cx43. The changes in Cx40 and Cx43 induced by Ang II were abolished by CNP through upregulation of phosphorylated AMP-activated kinase a1 (AMPK) and downregulation of TGF-β1. The effects of CNP on AMPK and TGF-β1 levels were inhibited by KT5823 and pertussis toxin, inhibitors of protein kinase G (PKG) and NP receptor type C (NPR-C), respectively. Thus, CNP can prevent Ang II-induced dysregulation of Cx40 and Cx43 through activation of AMPK via the CNP-PKG and CNP-NPR-C pathways in isolated beating rat atria. The present findings suggested that CNP may be therapeutically useful for clinical conditions involving cardiac dysregulation of Cx expression-related diseases.
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spelling pubmed-68545242019-11-21 C-type natriuretic peptide prevents angiotensin II-induced atrial connexin 40 and 43 dysregulation by activating AMP-activated kinase signaling Ding, Da-Zhi Jia, Ya-Nan Zhang, Bo Guan, Cheng-Ming Zhou, Shuai Li, Xiang Cui, Xun Mol Med Rep Articles C-type natriuretic peptide (CNP), from the family of natriuretic peptides (NPs), has been shown to induce antihypertrophic and antifibrotic effects in cardiomyocytes. However, the roles of CNP in the atrial dysregulation of connexin (Cx)40 and Cx43 remain to be elucidated. The present study aimed to investigate the effects of CNP on angiotensin (Ang) II-induced Cx40 and Cx43 dysregulation in isolated perfused beating rat left atria. A rat isolated perfused beating atrial model was used and the protein levels were determined via western blotting. Ang II significantly upregulated NF-κB, activator protein-1, transforming growth factor-β1 (TGF-β1), collagen I and matrix metalloproteinase 2, leading to atrial fibrosis, and downregulated expression of Cx40 and Cx43. The changes in Cx40 and Cx43 induced by Ang II were abolished by CNP through upregulation of phosphorylated AMP-activated kinase a1 (AMPK) and downregulation of TGF-β1. The effects of CNP on AMPK and TGF-β1 levels were inhibited by KT5823 and pertussis toxin, inhibitors of protein kinase G (PKG) and NP receptor type C (NPR-C), respectively. Thus, CNP can prevent Ang II-induced dysregulation of Cx40 and Cx43 through activation of AMPK via the CNP-PKG and CNP-NPR-C pathways in isolated beating rat atria. The present findings suggested that CNP may be therapeutically useful for clinical conditions involving cardiac dysregulation of Cx expression-related diseases. D.A. Spandidos 2019-12 2019-10-15 /pmc/articles/PMC6854524/ /pubmed/31638216 http://dx.doi.org/10.3892/mmr.2019.10744 Text en Copyright: © Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Ding, Da-Zhi
Jia, Ya-Nan
Zhang, Bo
Guan, Cheng-Ming
Zhou, Shuai
Li, Xiang
Cui, Xun
C-type natriuretic peptide prevents angiotensin II-induced atrial connexin 40 and 43 dysregulation by activating AMP-activated kinase signaling
title C-type natriuretic peptide prevents angiotensin II-induced atrial connexin 40 and 43 dysregulation by activating AMP-activated kinase signaling
title_full C-type natriuretic peptide prevents angiotensin II-induced atrial connexin 40 and 43 dysregulation by activating AMP-activated kinase signaling
title_fullStr C-type natriuretic peptide prevents angiotensin II-induced atrial connexin 40 and 43 dysregulation by activating AMP-activated kinase signaling
title_full_unstemmed C-type natriuretic peptide prevents angiotensin II-induced atrial connexin 40 and 43 dysregulation by activating AMP-activated kinase signaling
title_short C-type natriuretic peptide prevents angiotensin II-induced atrial connexin 40 and 43 dysregulation by activating AMP-activated kinase signaling
title_sort c-type natriuretic peptide prevents angiotensin ii-induced atrial connexin 40 and 43 dysregulation by activating amp-activated kinase signaling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854524/
https://www.ncbi.nlm.nih.gov/pubmed/31638216
http://dx.doi.org/10.3892/mmr.2019.10744
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