Oxidative Stress Causes Heart Failure with Impaired Mitochondrial Respiration
Open accessAbstract
Elderly people insidiously manifest the symptoms of heart failure, such as dyspnea and/or physical disabilities in an age-dependent manner. Although previous studies suggested that oxidative stress plays a pathological role in the development of heart failure, no direct evidence has been documented so far. In order to investigate the pathological significance of oxidative stress in the heart, we generated heart/muscle-specific manganese superoxide dismutase-deficient mice. The mutant mice developed progressive congestive heart failure with specific molecular defects in mitochondrial respiration. In this paper, we showed for the first time that the oxidative stress caused specific morphological changes of mitochondria, excess formation of superoxide (O(2)(*)(-)), reduction of ATP, and transcriptional alterations of genes associated with heart failure in respect to cardiac contractility. Accordingly, administration of a superoxide dismutase mimetic significantly ameliorated the symptoms. These results implied that O(2)(*)(-) generated in mitochondria played a pivotal role in the development and progression of heart failure. We here present a bona fide model for human cardiac failure with oxidative stress valuable for therapeutic interventions.
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NOX1 expression is activated by several factors including angiotensin II, PDGF, and thrombin.
“NOX1 expression is activated by several factors including angiotensin II, PDGF, and thrombin (382, 492, 630, 695, 999).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [695]
NOXA1 has been associated with atherosclerotic injury, with overexpression of NOXA1 increasing ROS production and increased NOXA1 levels detected in atherosclerotic lesions.
“NOXA1 has been also associated with atherosclerotic injury, with overexpression of NOXA1 increasing ROS production and increased NOXA1 levels detected in atherosclerotic lesions (695).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [695]
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- Authors
- Nojiri, H., Shimizu, T., Funakoshi, M., Yamaguchi, O., Zhou, H., Kawakami, S., Ohta, Y., Sami, M., Tachibana, T., Ishikawa, H., Kurosawa, H., Kahn, R. C., Otsu, K., & Shirasawa, T.
- Affiliations
- Juntendo University (JP)
- Tokyo Metropolitan Institute of Gerontology (JP)
- The University of Osaka (JP)
- Asahi Breweries (Japan) (JP)
- Jikei University School of Medicine (JP)
- Joslin Diabetes Center (US)
- Corresponding author
- Shirasawa, Takuji
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 281
- Issue
- 44
- Pages
- 33789-33801
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2075240899
- Cited by
- 230
- References
- 45
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 11 · 2020: 11 · 2019: 13 · 2018: 13 · 2017: 16 · 2016: 11 · 2015: 10 · 2014: 21 · 2013: 11 · 2012: 21
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- oxidative stress, heart failure, mitochondrial respiration, superoxide, manganese superoxide dismutase, mitochondrial morphology, ATP depletion, cardiac contractility, superoxide dismutase mimetic
- MeSH terms
- Superoxide Dismutase 2, Animals, Gene Expression Regulation, Heart Diseases, Mitochondria, Heart, Superoxide Dismutase, Transcription, Genetic, Lipid Peroxidation, Apoptosis, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, Disease Progression, Muscle, Skeletal, Microscopy, Electron, Transmission, Mice
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