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TLR9 is essential for HMGB1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis

The poor prognosis of patients with acute myocardial infarction is partially attributed to a large number of cardiomyocyte apoptosis, necrosis, limited cardiac healing and angiogenesis, and cardiac dysfunction. Immune cells dysfunction leads to nonhealing or poor healing of wounds after acute myocar...

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Autores principales: Liu, Fang-Yuan, Fan, Di, Yang, Zheng, Tang, Nan, Guo, Zhen, Ma, Shu-Qing, Ma, Zhen-Guo, Wu, Hai-Ming, Deng, Wei, Tang, Qi-Zhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579765/
https://www.ncbi.nlm.nih.gov/pubmed/31209243
http://dx.doi.org/10.1038/s41419-019-1718-7
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author Liu, Fang-Yuan
Fan, Di
Yang, Zheng
Tang, Nan
Guo, Zhen
Ma, Shu-Qing
Ma, Zhen-Guo
Wu, Hai-Ming
Deng, Wei
Tang, Qi-Zhu
author_facet Liu, Fang-Yuan
Fan, Di
Yang, Zheng
Tang, Nan
Guo, Zhen
Ma, Shu-Qing
Ma, Zhen-Guo
Wu, Hai-Ming
Deng, Wei
Tang, Qi-Zhu
author_sort Liu, Fang-Yuan
collection PubMed
description The poor prognosis of patients with acute myocardial infarction is partially attributed to a large number of cardiomyocyte apoptosis, necrosis, limited cardiac healing and angiogenesis, and cardiac dysfunction. Immune cells dysfunction leads to nonhealing or poor healing of wounds after acute myocardial infarction. Toll-like receptor 9 (TLR9) as an essential part of the innate immune system plays a vital role in regulating cardiomyocyte survival and wound healing. During hypoxia, High Mobility Group Box 1 (HMGB1), as the typical damage-associated molecular patterns (DAMPs) or alarmin, is rapidly released extracellularly and translocates from the nucleus to bind with cytoplasmic TLR9. However, the mechanism by which TLR9 interacts with HMGB1 and regulates myocardial damage remains unclear. Our current study found that the survival rate of TLR9KO mice with a higher rate of cardiac rupture was significantly lower than that in WT mice after 28 days post-operation. The effect of TLR9 knockout on insufficient wound healing in experimental MI was caused by a diminished number of myofibroblast and defective matrix synthetic capability. Moreover, the increased myocardial apoptotic cells and decreased angiogenic capacity were found in TLR9 knockout mice after MI. The results showed contrary in Recombinant Human High Mobility Group Box 1 (rhHMGB1) treated WT mice and similarity after applying rhHMGB1 in TLR9KO mice. This study demonstrates that TLR9 is essential for the repair of infarcted myocardium and interaction of HMGB1 and TLR9 is involved in the survival of myocardial cells, wound healing, and angiogenesis after myocardial infarction.
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spelling pubmed-65797652019-06-21 TLR9 is essential for HMGB1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis Liu, Fang-Yuan Fan, Di Yang, Zheng Tang, Nan Guo, Zhen Ma, Shu-Qing Ma, Zhen-Guo Wu, Hai-Ming Deng, Wei Tang, Qi-Zhu Cell Death Dis Article The poor prognosis of patients with acute myocardial infarction is partially attributed to a large number of cardiomyocyte apoptosis, necrosis, limited cardiac healing and angiogenesis, and cardiac dysfunction. Immune cells dysfunction leads to nonhealing or poor healing of wounds after acute myocardial infarction. Toll-like receptor 9 (TLR9) as an essential part of the innate immune system plays a vital role in regulating cardiomyocyte survival and wound healing. During hypoxia, High Mobility Group Box 1 (HMGB1), as the typical damage-associated molecular patterns (DAMPs) or alarmin, is rapidly released extracellularly and translocates from the nucleus to bind with cytoplasmic TLR9. However, the mechanism by which TLR9 interacts with HMGB1 and regulates myocardial damage remains unclear. Our current study found that the survival rate of TLR9KO mice with a higher rate of cardiac rupture was significantly lower than that in WT mice after 28 days post-operation. The effect of TLR9 knockout on insufficient wound healing in experimental MI was caused by a diminished number of myofibroblast and defective matrix synthetic capability. Moreover, the increased myocardial apoptotic cells and decreased angiogenic capacity were found in TLR9 knockout mice after MI. The results showed contrary in Recombinant Human High Mobility Group Box 1 (rhHMGB1) treated WT mice and similarity after applying rhHMGB1 in TLR9KO mice. This study demonstrates that TLR9 is essential for the repair of infarcted myocardium and interaction of HMGB1 and TLR9 is involved in the survival of myocardial cells, wound healing, and angiogenesis after myocardial infarction. Nature Publishing Group UK 2019-06-17 /pmc/articles/PMC6579765/ /pubmed/31209243 http://dx.doi.org/10.1038/s41419-019-1718-7 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
Liu, Fang-Yuan
Fan, Di
Yang, Zheng
Tang, Nan
Guo, Zhen
Ma, Shu-Qing
Ma, Zhen-Guo
Wu, Hai-Ming
Deng, Wei
Tang, Qi-Zhu
TLR9 is essential for HMGB1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis
title TLR9 is essential for HMGB1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis
title_full TLR9 is essential for HMGB1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis
title_fullStr TLR9 is essential for HMGB1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis
title_full_unstemmed TLR9 is essential for HMGB1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis
title_short TLR9 is essential for HMGB1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis
title_sort tlr9 is essential for hmgb1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579765/
https://www.ncbi.nlm.nih.gov/pubmed/31209243
http://dx.doi.org/10.1038/s41419-019-1718-7
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