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The Janus face of HMGB1 in heart disease: a necessary update

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein involved in transcription regulation, DNA replication and repair and nucleosome assembly. HMGB1 is passively released by necrotic tissues or actively secreted by stressed cells. Extracellular HMGB1 acts as a damage-associated molecula...

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Autores principales: Raucci, Angela, Di Maggio, Stefania, Scavello, Francesco, D’Ambrosio, Alessandro, Bianchi, Marco E., Capogrossi, Maurizio C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339675/
https://www.ncbi.nlm.nih.gov/pubmed/30306212
http://dx.doi.org/10.1007/s00018-018-2930-9
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author Raucci, Angela
Di Maggio, Stefania
Scavello, Francesco
D’Ambrosio, Alessandro
Bianchi, Marco E.
Capogrossi, Maurizio C.
author_facet Raucci, Angela
Di Maggio, Stefania
Scavello, Francesco
D’Ambrosio, Alessandro
Bianchi, Marco E.
Capogrossi, Maurizio C.
author_sort Raucci, Angela
collection PubMed
description High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein involved in transcription regulation, DNA replication and repair and nucleosome assembly. HMGB1 is passively released by necrotic tissues or actively secreted by stressed cells. Extracellular HMGB1 acts as a damage-associated molecular pattern (DAMPs) molecule and gives rise to several redox forms that by binding to different receptors and interactors promote a variety of cellular responses, including tissue inflammation or regeneration. Inhibition of extracellular HMGB1 in experimental models of myocardial ischemia/reperfusion injury, myocarditis, cardiomyopathies induced by mechanical stress, diabetes, bacterial infection or chemotherapeutic drugs reduces inflammation and is protective. In contrast, administration of HMGB1 after myocardial infarction induced by permanent coronary artery ligation ameliorates cardiac performance by promoting tissue regeneration. HMGB1 decreases contractility and induces hypertrophy and apoptosis in cardiomyocytes, stimulates cardiac fibroblast activities, and promotes cardiac stem cell proliferation and differentiation. Interestingly, maintenance of appropriate nuclear HMGB1 levels protects cardiomyocytes from apoptosis by preventing DNA oxidative stress, and mice with HMGB1cardiomyocyte-specific overexpression are partially protected from cardiac damage. Finally, higher levels of circulating HMGB1 are associated to human heart diseases. Hence, during cardiac injury, HMGB1 elicits both harmful and beneficial responses that may in part depend on the generation and stability of the diverse redox forms, whose specific functions in this context remain mostly unexplored. This review summarizes recent findings on HMGB1 biology and heart dysfunctions and discusses the therapeutic potential of modulating its expression, localization, and oxidative-dependent activities.
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spelling pubmed-63396752019-02-01 The Janus face of HMGB1 in heart disease: a necessary update Raucci, Angela Di Maggio, Stefania Scavello, Francesco D’Ambrosio, Alessandro Bianchi, Marco E. Capogrossi, Maurizio C. Cell Mol Life Sci Review High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein involved in transcription regulation, DNA replication and repair and nucleosome assembly. HMGB1 is passively released by necrotic tissues or actively secreted by stressed cells. Extracellular HMGB1 acts as a damage-associated molecular pattern (DAMPs) molecule and gives rise to several redox forms that by binding to different receptors and interactors promote a variety of cellular responses, including tissue inflammation or regeneration. Inhibition of extracellular HMGB1 in experimental models of myocardial ischemia/reperfusion injury, myocarditis, cardiomyopathies induced by mechanical stress, diabetes, bacterial infection or chemotherapeutic drugs reduces inflammation and is protective. In contrast, administration of HMGB1 after myocardial infarction induced by permanent coronary artery ligation ameliorates cardiac performance by promoting tissue regeneration. HMGB1 decreases contractility and induces hypertrophy and apoptosis in cardiomyocytes, stimulates cardiac fibroblast activities, and promotes cardiac stem cell proliferation and differentiation. Interestingly, maintenance of appropriate nuclear HMGB1 levels protects cardiomyocytes from apoptosis by preventing DNA oxidative stress, and mice with HMGB1cardiomyocyte-specific overexpression are partially protected from cardiac damage. Finally, higher levels of circulating HMGB1 are associated to human heart diseases. Hence, during cardiac injury, HMGB1 elicits both harmful and beneficial responses that may in part depend on the generation and stability of the diverse redox forms, whose specific functions in this context remain mostly unexplored. This review summarizes recent findings on HMGB1 biology and heart dysfunctions and discusses the therapeutic potential of modulating its expression, localization, and oxidative-dependent activities. Springer International Publishing 2018-10-10 2019 /pmc/articles/PMC6339675/ /pubmed/30306212 http://dx.doi.org/10.1007/s00018-018-2930-9 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
spellingShingle Review
Raucci, Angela
Di Maggio, Stefania
Scavello, Francesco
D’Ambrosio, Alessandro
Bianchi, Marco E.
Capogrossi, Maurizio C.
The Janus face of HMGB1 in heart disease: a necessary update
title The Janus face of HMGB1 in heart disease: a necessary update
title_full The Janus face of HMGB1 in heart disease: a necessary update
title_fullStr The Janus face of HMGB1 in heart disease: a necessary update
title_full_unstemmed The Janus face of HMGB1 in heart disease: a necessary update
title_short The Janus face of HMGB1 in heart disease: a necessary update
title_sort janus face of hmgb1 in heart disease: a necessary update
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339675/
https://www.ncbi.nlm.nih.gov/pubmed/30306212
http://dx.doi.org/10.1007/s00018-018-2930-9
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