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Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure
Inflammation plays a key role in pressure overload‐induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High‐mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload‐induced cardiac injur...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759479/ https://www.ncbi.nlm.nih.gov/pubmed/26647902 http://dx.doi.org/10.1111/jcmm.12743 |
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author | Zhang, Lei Liu, Ming Jiang, Hong Yu, Ying Yu, Peng Tong, Rui Wu, Jian Zhang, Shuning Yao, Kang Zou, Yunzeng Ge, Junbo |
author_facet | Zhang, Lei Liu, Ming Jiang, Hong Yu, Ying Yu, Peng Tong, Rui Wu, Jian Zhang, Shuning Yao, Kang Zou, Yunzeng Ge, Junbo |
author_sort | Zhang, Lei |
collection | PubMed |
description | Inflammation plays a key role in pressure overload‐induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High‐mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload‐induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild‐type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin‐embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC‐induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up‐regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload‐induced cardiac hypertrophy and cardiac dysfunction. |
format | Online Article Text |
id | pubmed-4759479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47594792016-03-01 Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure Zhang, Lei Liu, Ming Jiang, Hong Yu, Ying Yu, Peng Tong, Rui Wu, Jian Zhang, Shuning Yao, Kang Zou, Yunzeng Ge, Junbo J Cell Mol Med Original Articles Inflammation plays a key role in pressure overload‐induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High‐mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload‐induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild‐type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin‐embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC‐induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up‐regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload‐induced cardiac hypertrophy and cardiac dysfunction. John Wiley and Sons Inc. 2015-12-09 2016-03 /pmc/articles/PMC4759479/ /pubmed/26647902 http://dx.doi.org/10.1111/jcmm.12743 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zhang, Lei Liu, Ming Jiang, Hong Yu, Ying Yu, Peng Tong, Rui Wu, Jian Zhang, Shuning Yao, Kang Zou, Yunzeng Ge, Junbo Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure |
title | Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure |
title_full | Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure |
title_fullStr | Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure |
title_full_unstemmed | Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure |
title_short | Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure |
title_sort | extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759479/ https://www.ncbi.nlm.nih.gov/pubmed/26647902 http://dx.doi.org/10.1111/jcmm.12743 |
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