ArticleProceedings of the National Academy of Sciences of the United States of America2010
NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 395 papers.
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Who cites it
395 citing papers in PubMed, 766 citations in OpenAlex.
- Treatment with the Nox1/4 inhibitor Setanaxib ameliorates cardiac function in mouse models of Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Mitochondrial Distress Signals at the Heart-Liver Interface: Molecular Links Between MASLD and Heart Failure.International journal of molecular sciences · 2026Review
- Role of β-adrenergic signaling in the development of Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice.Scientific reports · 2026Article
- Chamber-specific cardiac proteome remodeling in a Göttingen minipig model of obesity and diabetes.Cardiovascular diabetology · 2026Article
- A decline in skeletal muscle NOX4 abrogates exercise-induced adaptive homeostasis and exacerbates biological aging.Science advances · 2026Article
- Bayes Syndrome and Myocardial Fibrosis: Mechanistic Links and Clinical Implications.Reviews in cardiovascular medicine · 2026Review
- Viral Comorbidities Remodel Host Transcriptome and Redox Signaling in an NADPH Oxidase Isoform-Specific Manner.Viruses · 2026Review
- Systems Biology Identifies TARS2 as a Cardiomyocyte Regulator of Mitochondrial Oxidative Stress in Dilated Cardiomyopathy.JACC. Basic to translational science · 2026Article
- Review
- Binge drinking as a potential cardiometabolic risk factor during adolescence in rats: novel protective antinitrosative mechanism of folic acid via caveolin-1.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- The brain and heart-axis in neurodegeneration and cardiovascular disease.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Mitochondrial dysfunction in hypertension: mechanistic pathways and therapeutic implications.Functional & integrative genomics · 2026Review
- Targeting the undruggable transcription factor, KLF5, with a peptidomimetic small molecule, NC114, attenuates pressure overload-induced cardiac remodeling and fibrosis.Scientific reports · 2026Article
- Disulfidptosis in heart failure: an emerging mechanism awaiting exploration.Frontiers in cardiovascular medicine · 2026Review
- From Defense to Disease: NADPH Oxidase in Cellular Function and Dysregulation.Journal of immunology research · 2026Review
- Gene and drug-mediated SERCA2a activation restores cardiac function and metabolic balance in diabetic mice.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Transcription factor MITF regulates masseter muscle growth and development.Physiological reports · 2025Article
- Targeting Inflammation: Cytosporone B Modulates Imatinib-Driven Biochemical Alterations in Rat Heart.International journal of molecular sciences · 2025Article
- The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling.Antioxidants (Basel, Switzerland) · 2025Review
335 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
NAD(P)H oxidases (Noxs) produce O(2)(-) and play an important role in cardiovascular pathophysiology. The Nox4 isoform is expressed primarily in the mitochondria in cardiac myocytes. To elucidate the function of endogenous Nox4 in the heart, we generated cardiac-specific Nox4(-/-) (c-Nox4(-/-)) mice. Nox4 expression was inhibited in c-Nox4(-/-) mice in a heart-specific manner, and there was no compensatory up-regulation in other Nox enzymes. These mice exhibited reduced levels of O(2)(-) in the heart, indicating that Nox4 is a significant source of O(2)(-) in cardiac myocytes. The baseline cardiac phenotype was normal in young c-Nox4(-/-) mice. In response to pressure overload (PO), however, increases in Nox4 expression and O(2)(-) production in mitochondria were abolished in c-Nox4(-/-) mice, and c-Nox4(-/-) mice exhibited significantly attenuated cardiac hypertrophy, interstitial fibrosis and apoptosis, and better cardiac function compared with WT mice. Mitochondrial swelling, cytochrome c release, and decreases in both mitochondrial DNA and aconitase activity in response to PO were attenuated in c-Nox4(-/-) mice. On the other hand, overexpression of Nox4 in mouse hearts exacerbated cardiac dysfunction, fibrosis, and apoptosis in response to PO. These results suggest that Nox4 in cardiac myocytes is a major source of mitochondrial oxidative stress, thereby mediating mitochondrial and cardiac dysfunction during PO.
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Registered trials
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