ArticleJournal of cellular physiology2016
The Nox1/4 Dual Inhibitor GKT137831 or Nox4 Knockdown Inhibits Angiotensin-II-Induced Adult Mouse Cardiac Fibroblast Proliferation and Migration. AT1 Physically Associates With Nox4.
Article in Journal of cellular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Computational modeling identifies protective mechanisms of estrogen and testosterone against atrial fibrosis.American journal of physiology. Heart and circulatory physiology · 2026Article
- An Angiotensin II Receptor Blocker Suppresses Glucose-Induced Oxidative Stress in Human Rotator Cuff-Derived Cells.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling.Antioxidants (Basel, Switzerland) · 2025Review
- Transient angiotensin-converting enzyme inhibition confers sex-specific protection against angiotensin II-induced cardiac remodeling.American journal of physiology. Cell physiology · 2025Article
- Oxidative Stress in Kidney Injury and Hypertension.Antioxidants (Basel, Switzerland) · 2024Review
- Phylogenetic conservation of the interdependent homeostatic relationship of sleep regulation and redox metabolism.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2024Review
- Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice.Scientific reports · 2023Article
- NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2023Review
- Intercellular model predicts mechanisms of inflammation-fibrosis coupling after myocardial infarction.The Journal of physiology · 2023Article
- Role of c-Src and reactive oxygen species in cardiovascular diseases.Molecular genetics and genomics : MGG · 2023Review
- Article
- Empagliflozin Reverses Oxidized LDL-Induced RECK Suppression, Cardiotrophin-1 Expression, MMP Activation, and Human Aortic Smooth Muscle Cell Proliferation and Migration.Mediators of inflammation · 2023Article
- NOX4 inhibition promotes the remodeling of dystrophic muscle.JCI insight · 2022Article
- Effects of Empagliflozin on Intermittent Hypoxia-Induced TRAF3IP2-Dependent Human Aortic Smooth Muscle Cell Proliferation.Medical research archives · 2022Article
- The Scientific Rationale for the Introduction of Renalase in the Concept of Cardiac Fibrosis.Frontiers in cardiovascular medicine · 2022Review
- The Molecular Mechanism of Aerobic Exercise Improving Vascular Remodeling in Hypertension.Frontiers in physiology · 2022Review
- The Impact of microRNAs in Renin-Angiotensin-System-Induced Cardiac Remodelling.International journal of molecular sciences · 2021Review
- RAS inhibition in resident fibroblast biology.Cellular signalling · 2021Review
- Long-term exposure to a hypomagnetic field attenuates adult hippocampal neurogenesis and cognition.Nature communications · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse cardiac fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2 O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attenuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse cardiac remodeling.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.