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The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease

The ASK1-signalosome→p38 MAPK and SAPK/JNK signaling networks promote senescence (in vitro) and aging (in vivo, animal models and human cohorts) in response to oxidative stress and inflammation. These networks contribute to the promotion of age-associated cardiovascular diseases of oxidative stress...

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Autor principal: Papaconstantinou, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912541/
https://www.ncbi.nlm.nih.gov/pubmed/31689891
http://dx.doi.org/10.3390/cells8111383
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author Papaconstantinou, John
author_facet Papaconstantinou, John
author_sort Papaconstantinou, John
collection PubMed
description The ASK1-signalosome→p38 MAPK and SAPK/JNK signaling networks promote senescence (in vitro) and aging (in vivo, animal models and human cohorts) in response to oxidative stress and inflammation. These networks contribute to the promotion of age-associated cardiovascular diseases of oxidative stress and inflammation. Furthermore, their inhibition delays the onset of these cardiovascular diseases as well as senescence and aging. In this review we focus on whether the (a) ASK1-signalosome, a major center of distribution of reactive oxygen species (ROS)-mediated stress signals, plays a role in the promotion of cardiovascular diseases of oxidative stress and inflammation; (b) The ASK1-signalosome links ROS signals generated by dysfunctional mitochondrial electron transport chain complexes to the p38 MAPK stress response pathway; (c) the pathway contributes to the sensitivity and vulnerability of aged tissues to diseases of oxidative stress; and (d) the importance of inhibitors of these pathways to the development of cardioprotection and pharmaceutical interventions. We propose that the ASK1-signalosome regulates the progression of cardiovascular diseases. The resultant attenuation of the physiological characteristics of cardiomyopathies and aging by inhibition of the ASK1-signalosome network lends support to this conclusion. Importantly the ROS-mediated activation of the ASK1-signalosome p38 MAPK pathway suggests it is a major center of dissemination of the ROS signals that promote senescence, aging and cardiovascular diseases. Pharmacological intervention is, therefore, feasible through the continued identification of potent, non-toxic small molecule inhibitors of either ASK1 or p38 MAPK activity. This is a fruitful future approach to the attenuation of physiological aspects of mammalian cardiomyopathies and aging.
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spelling pubmed-69125412020-01-02 The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease Papaconstantinou, John Cells Review The ASK1-signalosome→p38 MAPK and SAPK/JNK signaling networks promote senescence (in vitro) and aging (in vivo, animal models and human cohorts) in response to oxidative stress and inflammation. These networks contribute to the promotion of age-associated cardiovascular diseases of oxidative stress and inflammation. Furthermore, their inhibition delays the onset of these cardiovascular diseases as well as senescence and aging. In this review we focus on whether the (a) ASK1-signalosome, a major center of distribution of reactive oxygen species (ROS)-mediated stress signals, plays a role in the promotion of cardiovascular diseases of oxidative stress and inflammation; (b) The ASK1-signalosome links ROS signals generated by dysfunctional mitochondrial electron transport chain complexes to the p38 MAPK stress response pathway; (c) the pathway contributes to the sensitivity and vulnerability of aged tissues to diseases of oxidative stress; and (d) the importance of inhibitors of these pathways to the development of cardioprotection and pharmaceutical interventions. We propose that the ASK1-signalosome regulates the progression of cardiovascular diseases. The resultant attenuation of the physiological characteristics of cardiomyopathies and aging by inhibition of the ASK1-signalosome network lends support to this conclusion. Importantly the ROS-mediated activation of the ASK1-signalosome p38 MAPK pathway suggests it is a major center of dissemination of the ROS signals that promote senescence, aging and cardiovascular diseases. Pharmacological intervention is, therefore, feasible through the continued identification of potent, non-toxic small molecule inhibitors of either ASK1 or p38 MAPK activity. This is a fruitful future approach to the attenuation of physiological aspects of mammalian cardiomyopathies and aging. MDPI 2019-11-04 /pmc/articles/PMC6912541/ /pubmed/31689891 http://dx.doi.org/10.3390/cells8111383 Text en © 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Papaconstantinou, John
The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease
title The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease
title_full The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease
title_fullStr The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease
title_full_unstemmed The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease
title_short The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease
title_sort role of signaling pathways of inflammation and oxidative stress in development of senescence and aging phenotypes in cardiovascular disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912541/
https://www.ncbi.nlm.nih.gov/pubmed/31689891
http://dx.doi.org/10.3390/cells8111383
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