ArticleCardiovascular research2013
TGF-β signalling and reactive oxygen species drive fibrosis and matrix remodelling in myxomatous mitral valves.
Article in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
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.
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.
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Who cites it
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 137 citations in OpenAlex.
- The Role of Transforming Growth Factor-β Signaling in Myxomatous Mitral Valve Degeneration.Frontiers in cardiovascular medicine · 2022Pooled it
- Genomic analysis in patients with myxomatous mitral valve prolapse: current state of knowledge.BMC cardiovascular disorders · 2018Pooled it
- Circulating Biomarkers Related to Mitral Valve Prolapse: Current Evidence and Mechanistic Perspective.Current cardiology reports · 2026Review
- Lymphatic therapies open the valve in Marfan syndrome.The Journal of clinical investigation · 2026Article
- Hexavalent Chromium Exposure Disrupts Cardiac Development in Chicken Embryos Through Oxidative Stress and Activation of TGFβ1/COL3A1 Pathway in Chick Embryos.Cardiovascular toxicology · 2026Article
- Minimally Invasive, Echocardiography-Guided Mouse Model of Degenerative Mitral Regurgitation Recapitulates Cardiac Remodeling and Arrhythmogenesis.Journal of the American Heart Association · 2026Article
- ZFP36 inhibits the pro-apoptotic effects of transforming growth factor β1 on mitral valve interstitial cells via the GTP-binding protein 6 pathway in mitral valve prolapse.Experimental physiology · 2026Article
- Floppy Mitral Valve/Mitral Valve Prolapse: Diagnosis and Clinical Classification in This Continuing Odyssey.European cardiology · 2026Review
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- Chronic Mitral Valve Fibrosis in Rheumatic Heart Disease: From Immune Trigger to Inflammatory and Mechanical Progression.Journal of the American Heart Association · 2025Review
- The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- Hemodynamic forces prevent myxomatous valve disease in mice through KLF2/4 signaling.The Journal of clinical investigation · 2025Article
- Reversed Remodeling Unveils Mitral Annular Disjunction.JACC. Case reports · 2025Article
- Unveiling the Angiogenic Potential and Functional Decline of Valve Interstitial Cells During Calcific Aortic Valve Stenosis Progression.Journal of cellular and molecular medicine · 2025Article
- Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation.Antioxidants (Basel, Switzerland) · 2024Review
- Monoamine Oxidase Contributes to Valvular Oxidative Stress: A Prospective Observational Pilot Study in Patients with Severe Mitral Regurgitation.International journal of molecular sciences · 2024Observational
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Defining the Role of the miR-145-KLF4-αSMA Axis in Mitral Valvular Interstitial Cell Activation in Myxomatous Mitral Valve Prolapse Using the Canine Model.International journal of molecular sciences · 2024Article
- Safety and efficacy of canine gonadal tissue-derived mesenchymal stem cells for early myxomatous mitral valve disease.Frontiers in veterinary science · 2024Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
aimsMyxomatous mitral valve disease (MMVD) is associated with leaflet thickening, fibrosis, matrix remodelling, and leaflet prolapse. Molecular mechanisms contributing to MMVD, however, remain poorly understood. We tested the hypothesis that increased transforming growth factor-β (TGF-β) signalling and reactive oxygen species (ROS) are major contributors to pro-fibrotic gene expression in human and mouse mitral valves. METHODS AND
resultsUsing qRT-PCR, we found that increased expression of TGF-β1 in mitral valves from humans with MMVD (n = 24) was associated with increased expression of connective tissue growth factor (CTGF) and matrix metalloproteinase 2 (MMP2). Increased levels of phospho-SMAD2/3 (western blotting) and expression of SMAD-specific E3 ubiquitin-protein ligases (SMURF) 1 and 2 (qRT-PCR) suggested that TGF-β1 signalling occurred through canonical signalling cascades. Oxidative stress (dihydroethidium staining) was increased in human MMVD tissue and associated with increases in NAD(P)H oxidase catalytic subunits (Nox) 2 and 4, occurring despite increases in superoxide dismutase 1 (SOD1). In mitral valves from SOD1-deficient mice, expression of CTGF, MMP2, Nox2, and Nox4 was significantly increased, suggesting that ROS can independently activate pro-fibrotic and matrix remodelling gene expression patterns. Furthermore, treatment of mouse mitral valve interstitial cells with cell permeable antioxidants attenuated TGF-β1-induced pro-fibrotic and matrix remodelling gene expression in vitro.
conclusionActivation of canonical TGF-β signalling is a major contributor to fibrosis and matrix remodelling in MMVD, and is amplified by increases in oxidative stress. Treatments aimed at reducing TGF-β activation and oxidative stress in early MMVD may slow progression of MMVD.
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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.