ArticleOncotarget2016
NOX4 downregulation leads to senescence of human vascular smooth muscle cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
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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.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Mechanisms of Doxorubicin-Induced Cardiac Senescence and Potential Therapeutic Strategies.Biomolecules · 2026Review
- Review
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- A Signature of Senescence Based on An Analysis of Selected Markers in Primary Vascular Smooth Muscle Cells Cultured In Vitro and Derived from Atherosclerotic Plaque.Aging and disease · 2025Article
- Article
- Redox signaling in impaired cascades of wound healing: promising approach.Molecular biology reports · 2023Review
- RecQ dysfunction contributes to social and depressive-like behavior and affects aldolase activity in mice.Neurobiology of disease · 2023Article
- Fiji-Based Tool for Rapid and Unbiased Analysis of SA-β-Gal Activity in Cultured Cells.Biomolecules · 2023Article
- Understanding the Protective Role of Exosomes in Doxorubicin-Induced Cardiotoxicity.Oxidative medicine and cellular longevity · 2022Review
- Non-coding RNAs in cancer therapy-induced cardiotoxicity: Mechanisms, biomarkers, and treatments.Frontiers in cardiovascular medicine · 2022Review
- Review
- Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence.Pharmacology & therapeutics · 2021Review
- Inhibition of NADPH Oxidases Activity by Diphenyleneiodonium Chloride as a Mechanism of Senescence Induction in Human Cancer Cells.Antioxidants (Basel, Switzerland) · 2020Article
- Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020Review
- Klf5 down-regulation induces vascular senescence through eIF5a depletion and mitochondrial fission.PLoS biology · 2020Article
- Butyrate mitigates TNF-α-induced attachment of monocytes to endothelial cells.Journal of bioenergetics and biomembranes · 2020Article
- Nicotine in Senescence and Atherosclerosis.Cells · 2020Review
- Inflammation as a mediator of arterial ageing.Experimental physiology · 2019Review
- Reactive Oxygen Species Signaling Promotes Hypoxia-Inducible Factor 1α Stabilization in Sonic Hedgehog-Driven Cerebellar Progenitor Cell Proliferation.Molecular and cellular biology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senescence is a stress response characterized by an irreversible growth arrest and alterations in certain cell functions. It is believed that both double-strand DNA breaks (DSB) and increased ROS level are the main culprit of senescence. Excessive ROS production is also particularly important in the development of a number of cardiovascular disorders. In this context the involvement of professional ROS-producing enzymes, NADPH oxidases (NOX), was postulated. In contrary to the common knowledge, we have shown that not only increased ROS production but also diminished ROS level could be involved in the induction of senescence.Accordingly, our studies revealed that stress-induced premature senescence (SIPS) of vascular smooth muscle cells (VSMCs) induced by doxorubicin or H2O2, correlates with increased level of DSB and ROS. On the other hand, both SIPS and replicative senescence were accompanied by diminished expression of NOX4. Moreover, inhibition of NOX activity or decrease of NOX4 expression led to permanent growth arrest of VSMCs and secretion of interleukins and VEGF. Interestingly, cells undergoing senescence due to NOX4 depletion neither acquired DSB nor activated DNA damage response. Instead, transient induction of the p27, upregulation of HIF-1alpha, decreased expression of cyclin D1 and hypophosphorylated Rb was observed. Our results showed that lowering the level of ROS-producing enzyme - NOX4 oxidase below physiological level leads to cellular senescence of VSMCs which is correlated with secretion of pro-inflammatory cytokines. Thus the use of specific NOX4 inhibitors for pharmacotherapy of vascular diseases should be carefully considered.
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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.