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Involvement of NADPH oxidase in age-associated cardiac remodeling
Increased activation of the renin–angiotensin–aldosterone system (RAAS) and an increase in oxidative stress are both implicated in age-related cardiac remodeling but their precise interrelationship and linkage to underlying molecular and cellular abnormalities remain to be defined. Recent studies in...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Academic Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877878/ https://www.ncbi.nlm.nih.gov/pubmed/20079746 http://dx.doi.org/10.1016/j.yjmcc.2010.01.006 |
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author | Wang, Mingyi Zhang, Jing Walker, Simon J. Dworakowski, Rafal Lakatta, Edward G. Shah, Ajay M. |
author_facet | Wang, Mingyi Zhang, Jing Walker, Simon J. Dworakowski, Rafal Lakatta, Edward G. Shah, Ajay M. |
author_sort | Wang, Mingyi |
collection | PubMed |
description | Increased activation of the renin–angiotensin–aldosterone system (RAAS) and an increase in oxidative stress are both implicated in age-related cardiac remodeling but their precise interrelationship and linkage to underlying molecular and cellular abnormalities remain to be defined. Recent studies indicate that NADPH oxidases are major sources of oxidative stress and are activated by the RAAS. This study investigated the relationship between the NADPH oxidase system, age-related cardiac remodeling and its underlying mechanisms. We studied male Fisher 344 cross Brown Norway rats aged 2 months (young rats), 8 months (young adult rats) or 30 months (old rats). Aging-dependent increases in blood pressure, cardiomyocyte area, coronary artery remodeling and cardiac fibrosis were associated with increased myocardial NADPH oxidase activity attributable to the Nox2 isoform. These changes were accompanied by evidence of local RAAS activation, increased expression of connective tissue growth factor (CTGF) and TGF-β1, and a significant activation of MMP-2 and MT1-MMP. The changes in old rats were replicated in 8 month old rats that were chronically treated with angiotensin II for 28 days. Increased RAAS activation may drive age-related cardiac remodeling through the activation of Nox2 NADPH oxidase and subsequent increases in MMP activation, fibrosis and cardiomyocyte hypertrophy. |
format | Text |
id | pubmed-2877878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Academic Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28778782010-06-10 Involvement of NADPH oxidase in age-associated cardiac remodeling Wang, Mingyi Zhang, Jing Walker, Simon J. Dworakowski, Rafal Lakatta, Edward G. Shah, Ajay M. J Mol Cell Cardiol Original Article Increased activation of the renin–angiotensin–aldosterone system (RAAS) and an increase in oxidative stress are both implicated in age-related cardiac remodeling but their precise interrelationship and linkage to underlying molecular and cellular abnormalities remain to be defined. Recent studies indicate that NADPH oxidases are major sources of oxidative stress and are activated by the RAAS. This study investigated the relationship between the NADPH oxidase system, age-related cardiac remodeling and its underlying mechanisms. We studied male Fisher 344 cross Brown Norway rats aged 2 months (young rats), 8 months (young adult rats) or 30 months (old rats). Aging-dependent increases in blood pressure, cardiomyocyte area, coronary artery remodeling and cardiac fibrosis were associated with increased myocardial NADPH oxidase activity attributable to the Nox2 isoform. These changes were accompanied by evidence of local RAAS activation, increased expression of connective tissue growth factor (CTGF) and TGF-β1, and a significant activation of MMP-2 and MT1-MMP. The changes in old rats were replicated in 8 month old rats that were chronically treated with angiotensin II for 28 days. Increased RAAS activation may drive age-related cardiac remodeling through the activation of Nox2 NADPH oxidase and subsequent increases in MMP activation, fibrosis and cardiomyocyte hypertrophy. Academic Press 2010-04 /pmc/articles/PMC2877878/ /pubmed/20079746 http://dx.doi.org/10.1016/j.yjmcc.2010.01.006 Text en © 2010 Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license |
spellingShingle | Original Article Wang, Mingyi Zhang, Jing Walker, Simon J. Dworakowski, Rafal Lakatta, Edward G. Shah, Ajay M. Involvement of NADPH oxidase in age-associated cardiac remodeling |
title | Involvement of NADPH oxidase in age-associated cardiac remodeling |
title_full | Involvement of NADPH oxidase in age-associated cardiac remodeling |
title_fullStr | Involvement of NADPH oxidase in age-associated cardiac remodeling |
title_full_unstemmed | Involvement of NADPH oxidase in age-associated cardiac remodeling |
title_short | Involvement of NADPH oxidase in age-associated cardiac remodeling |
title_sort | involvement of nadph oxidase in age-associated cardiac remodeling |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877878/ https://www.ncbi.nlm.nih.gov/pubmed/20079746 http://dx.doi.org/10.1016/j.yjmcc.2010.01.006 |
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