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The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143

Untreated pathological cardiac hypertrophy, which can be caused by sustained systemic hypertension, may lead to heart failure. In the present study, we investigated whether AS-1 had attenuating effects on hypertension-induced cardiac hypertrophy, and whether this process was mediated by the regulati...

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Autores principales: Song, Juan, Xie, Qifei, Wang, Lin, Lu, Yi, Liu, Peijing, Yang, Ping, Chen, Rui, Shao, Chen, Qiao, Chen, Wang, Zhongqun, Yan, Jinchuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478826/
https://www.ncbi.nlm.nih.gov/pubmed/31015570
http://dx.doi.org/10.1038/s41598-019-42936-x
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author Song, Juan
Xie, Qifei
Wang, Lin
Lu, Yi
Liu, Peijing
Yang, Ping
Chen, Rui
Shao, Chen
Qiao, Chen
Wang, Zhongqun
Yan, Jinchuan
author_facet Song, Juan
Xie, Qifei
Wang, Lin
Lu, Yi
Liu, Peijing
Yang, Ping
Chen, Rui
Shao, Chen
Qiao, Chen
Wang, Zhongqun
Yan, Jinchuan
author_sort Song, Juan
collection PubMed
description Untreated pathological cardiac hypertrophy, which can be caused by sustained systemic hypertension, may lead to heart failure. In the present study, we investigated whether AS-1 had attenuating effects on hypertension-induced cardiac hypertrophy, and whether this process was mediated by the regulation of miRNA-143. To induce the hypertrophic response in vitro, cardiomyocytes were stimulated with Ang II for 24hs. AS-1 administration strongly attenuated Ang II-induced hypertrophic response of cardiomyocytes. Chronical infusion of Ang II via implanted osmotic mini-pump induced increased blood pressure and cardiac hypertrophy in vivo. AS-1 administration attenuated hypertension-induced cardiac hypertrophy by, at least in part, inhibin of MAPK signaling. We observed, for the first time, upregulated expression of miRNA-143 in Ang II-induced cardiomyocytes, and inhibition of miRNA-143 significantly reduced the Ang II-induced hypertrophic responses. Importantly, AS-1 administration diminished the Ang II-induced upregulation of miRNA-143. Overexpression of miRNA-143 abolished the attenuating effects of AS-1 on Ang II-induced hypertrophic response of cardiomyocytes. Additionally, AS-1 administration abrogates Ang II-induced nuclear translocation of p50 NF-κB subunit in hypertrophic cardiomyocytes. Application of NF-κB inhibitor significantly suppressed Ang II-induced upregulation of miRNA-143. Our data suggest a novel mechanism by which AS-1 attenuates Ang II-induced hypertrophic response through downregulation miRNA-143 expression in a NF-κB-dependent manner.
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spelling pubmed-64788262019-05-03 The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143 Song, Juan Xie, Qifei Wang, Lin Lu, Yi Liu, Peijing Yang, Ping Chen, Rui Shao, Chen Qiao, Chen Wang, Zhongqun Yan, Jinchuan Sci Rep Article Untreated pathological cardiac hypertrophy, which can be caused by sustained systemic hypertension, may lead to heart failure. In the present study, we investigated whether AS-1 had attenuating effects on hypertension-induced cardiac hypertrophy, and whether this process was mediated by the regulation of miRNA-143. To induce the hypertrophic response in vitro, cardiomyocytes were stimulated with Ang II for 24hs. AS-1 administration strongly attenuated Ang II-induced hypertrophic response of cardiomyocytes. Chronical infusion of Ang II via implanted osmotic mini-pump induced increased blood pressure and cardiac hypertrophy in vivo. AS-1 administration attenuated hypertension-induced cardiac hypertrophy by, at least in part, inhibin of MAPK signaling. We observed, for the first time, upregulated expression of miRNA-143 in Ang II-induced cardiomyocytes, and inhibition of miRNA-143 significantly reduced the Ang II-induced hypertrophic responses. Importantly, AS-1 administration diminished the Ang II-induced upregulation of miRNA-143. Overexpression of miRNA-143 abolished the attenuating effects of AS-1 on Ang II-induced hypertrophic response of cardiomyocytes. Additionally, AS-1 administration abrogates Ang II-induced nuclear translocation of p50 NF-κB subunit in hypertrophic cardiomyocytes. Application of NF-κB inhibitor significantly suppressed Ang II-induced upregulation of miRNA-143. Our data suggest a novel mechanism by which AS-1 attenuates Ang II-induced hypertrophic response through downregulation miRNA-143 expression in a NF-κB-dependent manner. Nature Publishing Group UK 2019-04-23 /pmc/articles/PMC6478826/ /pubmed/31015570 http://dx.doi.org/10.1038/s41598-019-42936-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Song, Juan
Xie, Qifei
Wang, Lin
Lu, Yi
Liu, Peijing
Yang, Ping
Chen, Rui
Shao, Chen
Qiao, Chen
Wang, Zhongqun
Yan, Jinchuan
The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143
title The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143
title_full The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143
title_fullStr The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143
title_full_unstemmed The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143
title_short The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143
title_sort tir/bb-loop mimetic as-1 prevents ang ii-induced hypertensive cardiac hypertrophy via nf-κb dependent downregulation of mirna-143
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478826/
https://www.ncbi.nlm.nih.gov/pubmed/31015570
http://dx.doi.org/10.1038/s41598-019-42936-x
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