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Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload
Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2). An emerging idea that could explain these findings concerns the role of ele...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991908/ https://www.ncbi.nlm.nih.gov/pubmed/29885625 http://dx.doi.org/10.1016/j.redox.2018.05.016 |
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author | Dassanayaka, Sujith Zheng, Yuting Gibb, Andrew A. Cummins, Timothy D. McNally, Lindsey A. Brittian, Kenneth R. Jagatheesan, Ganapathy Audam, Timothy N. Long, Bethany W. Brainard, Robert E. Jones, Steven P. Hill, Bradford G. |
author_facet | Dassanayaka, Sujith Zheng, Yuting Gibb, Andrew A. Cummins, Timothy D. McNally, Lindsey A. Brittian, Kenneth R. Jagatheesan, Ganapathy Audam, Timothy N. Long, Bethany W. Brainard, Robert E. Jones, Steven P. Hill, Bradford G. |
author_sort | Dassanayaka, Sujith |
collection | PubMed |
description | Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2). An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC) for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. |
format | Online Article Text |
id | pubmed-5991908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-59919082018-06-11 Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload Dassanayaka, Sujith Zheng, Yuting Gibb, Andrew A. Cummins, Timothy D. McNally, Lindsey A. Brittian, Kenneth R. Jagatheesan, Ganapathy Audam, Timothy N. Long, Bethany W. Brainard, Robert E. Jones, Steven P. Hill, Bradford G. Redox Biol Research Paper Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2). An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC) for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Elsevier 2018-06-01 /pmc/articles/PMC5991908/ /pubmed/29885625 http://dx.doi.org/10.1016/j.redox.2018.05.016 Text en © 2018 Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Dassanayaka, Sujith Zheng, Yuting Gibb, Andrew A. Cummins, Timothy D. McNally, Lindsey A. Brittian, Kenneth R. Jagatheesan, Ganapathy Audam, Timothy N. Long, Bethany W. Brainard, Robert E. Jones, Steven P. Hill, Bradford G. Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload |
title | Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload |
title_full | Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload |
title_fullStr | Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload |
title_full_unstemmed | Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload |
title_short | Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload |
title_sort | cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991908/ https://www.ncbi.nlm.nih.gov/pubmed/29885625 http://dx.doi.org/10.1016/j.redox.2018.05.016 |
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