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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-07-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231718304117 |
| _version_ | 1818282025936748544 |
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| author | Sujith Dassanayaka Yuting Zheng Andrew A. Gibb Timothy D. Cummins Lindsey A. McNally Kenneth R. Brittian Ganapathy Jagatheesan Timothy N. Audam Bethany W. Long Robert E. Brainard Steven P. Jones Bradford G. Hill |
| author_facet | Sujith Dassanayaka Yuting Zheng Andrew A. Gibb Timothy D. Cummins Lindsey A. McNally Kenneth R. Brittian Ganapathy Jagatheesan Timothy N. Audam Bethany W. Long Robert E. Brainard Steven P. Jones Bradford G. Hill |
| author_sort | Sujith Dassanayaka |
| collection | DOAJ |
| 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. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesis |
| first_indexed | 2024-12-13T00:14:28Z |
| format | Article |
| id | doaj.art-26cadb1f9fa54a289fd9b0c378338d7a |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-13T00:14:28Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-26cadb1f9fa54a289fd9b0c378338d7a2022-12-22T00:05:50ZengElsevierRedox Biology2213-23172018-07-0117440449Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overloadSujith Dassanayaka0Yuting Zheng1Andrew A. Gibb2Timothy D. Cummins3Lindsey A. McNally4Kenneth R. Brittian5Ganapathy Jagatheesan6Timothy N. Audam7Bethany W. Long8Robert E. Brainard9Steven P. Jones10Bradford G. Hill11Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United StatesInstitute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United StatesInstitute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United StatesDivision of Nephrology and Hypertension, Department of Medicine, University of Louisville, Louisville, KY, United StatesInstitute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United StatesInstitute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United StatesInstitute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United StatesInstitute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United StatesInstitute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United StatesDepartment of Physiology, University of Louisville, Louisville, KY, United StatesInstitute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United StatesInstitute of Molecular Cardiology, University of Louisville, Louisville, KY, United States; Diabetes and Obesity Center, Division of Cardiovascular Medicine, University of Louisville, Louisville, KY, United States; Correspondence to: Diabetes and Obesity Center, Department of Cardiovascular Medicine, University of Louisville, 580 S. Preston St., Rm 321E, Louisville, KY 40202, United States.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. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesishttp://www.sciencedirect.com/science/article/pii/S2213231718304117 |
| spellingShingle | Sujith Dassanayaka Yuting Zheng Andrew A. Gibb Timothy D. Cummins Lindsey A. McNally Kenneth R. Brittian Ganapathy Jagatheesan Timothy N. Audam Bethany W. Long Robert E. Brainard Steven P. Jones Bradford G. Hill Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload Redox Biology |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S2213231718304117 |
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