ArticleCirculation2015
NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating Akt/mTOR and NFκB signaling pathways.
Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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Who cites it
160 citing papers in PubMed, 241 citations in OpenAlex.
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Hydroxytyrosol attenuates obesity-induced myocardial fibrosis by inhibiting NLRP3/CYLD/NOX4 mediated oxidative stress.NPJ science of food · 2026Article
- Exercise volume modulates cardiac protection in a type 2 diabetic rat model: differential effects of high- and low-volume moderate-intensity endurance exercise training on diabetic cardiomyopathy.Cardiovascular diabetology. Endocrinology reports · 2026Article
- Oxidative Stress in Diabetic Cardiomyopathy: Molecular Mechanisms and Emerging Therapeutic Targets.Biomolecules · 2026Review
- From Defense to Disease: NADPH Oxidase in Cellular Function and Dysregulation.Journal of immunology research · 2026Review
- Unraveling the interplay between RAS axes and NOX signaling in fibroblasts during cardiac fibrosis.Molecular and cellular biochemistry · 2026Review
- Pathogenic Role of mTOR Signaling in Cardiometabolic Disease: Implications for Heart, Liver, and Kidney Dysfunction.Physiological research · 2025Review
- Diabetic cardiomyopathy: Mechanistic insights on molecular pathways and emerging therapeutic approaches.Heart failure reviews · 2025Review
- ER-phagy Activation by AMFR Attenuates Cardiac Fibrosis Post-Myocardial Infarction via mTORC1 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Deletion of ZNRF2 Exacerbates MPTP-Induced Parkinson's Disease by Activating mTOR-Mediated Neuroinflammatory Pathways.Molecular neurobiology · 2025Article
- Biological Actions of Alamandine: A Scoping Review.Biomedicines · 2025Review
- Exploring Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) as a Potential Therapeutic Target for Cardiac Hypertrophy.ACS pharmacology & translational science · 2025Review
- Beyond conventional therapy: NOX4 as a promising target in cardiomyopathy.Molecular biology reports · 2025Review
- Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea.Antioxidants (Basel, Switzerland) · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- The role of myocardial fibrosis in the diabetic cardiomyopathy.Diabetology & metabolic syndrome · 2025Review
- Transient angiotensin-converting enzyme inhibition confers sex-specific protection against angiotensin II-induced cardiac remodeling.American journal of physiology. Cell physiology · 2025Article
- The mTOR Signaling Pathway: Key Regulator and Therapeutic Target for Heart Disease.Biomedicines · 2025Review
- 20-HETE mediates Ang II-induced cardiac hypertrophy via ROS and CaScientific reports · 2025Article
- Downregulation of PGAM2 alleviates angiotensin II-induced cardiac hypertrophy by destabilizing HSP90 and inactivating the mTOR/IKKα signaling pathway.International journal of biological sciences · 2025Article
100 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNADPH oxidase 4 (Nox4) has been implicated in cardiac remodeling, but its precise role in cardiac injury remains controversial. Furthermore, little is known about the downstream effector signaling pathways activated by Nox4-derived reactive oxygen species in the myocardium. We investigated the role of Nox4 and Nox4-associated signaling pathways in the development of cardiac remodeling. METHODS AND
resultsCardiac-specific human Nox4 transgenic mice (c-hNox4Tg) were generated. Four groups of mice were studied: (1) control mice, littermates that are negative for hNox4 transgene but Cre positive; (2) c-hNox4 Tg mice; (3) angiotensin II (AngII)-infused control mice; and (4) c-hNox4Tg mice infused with AngII. The c-hNox4Tg mice exhibited an ≈10-fold increase in Nox4 protein expression and an 8-fold increase in the production of reactive oxygen species, and manifested cardiac interstitial fibrosis. AngII infusion to control mice increased cardiac Nox4 expression and induced fibrosis and hypertrophy. The Tg mice receiving AngII exhibited more advanced cardiac remodeling and robust elevation in Nox4 expression, indicating that AngII worsens cardiac injury, at least in part by enhancing Nox4 expression. Moreover, hNox4 transgene and AngII infusion induced the expression of cardiac fetal genes and activated the Akt-mTOR and NFκB signaling pathways. Treatment of AngII-infused c-hNox4Tg mice with GKT137831, a Nox4/Nox1 inhibitor, abolished the increase in oxidative stress, suppressed the Akt-mTOR and NFκB signaling pathways, and attenuated cardiac remodeling.
conclusionsUpregulation of Nox4 in the myocardium causes cardiac remodeling through activating Akt-mTOR and NFκB signaling pathways. Inhibition of Nox4 has therapeutic potential to treat cardiac remodeling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.