ArticleCirculation. Cardiovascular genetics2015
Nonbiased Molecular Screening Identifies Novel Molecular Regulators of Fibrogenic and Proliferative Signaling in Myxomatous Mitral Valve Disease.
Article in Circulation. Cardiovascular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
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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
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 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
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- Genetic Basis of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniel Dogs-A Review.Veterinary sciences · 2025Review
- Involvement of TGF-β, mTOR, and inflammatory mediators in aging alterations during myxomatous mitral valve disease in a canine model.GeroScience · 2025Review
- Integrin-mediated mTOR signaling drives TGF-β overactivity and myxomatous mitral valve degeneration in hypomorphic fibrillin-1 mice.The Journal of clinical investigation · 2025Article
- Hemodynamic forces prevent myxomatous valve disease in mice through KLF2/4 signaling.The Journal of clinical investigation · 2025Article
- Article
- Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Mouse Congenital Myxomatous Valve Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Mendelian randomization reveals interactions of the blood proteome and immunome in mitral valve prolapse.Communications medicine · 2024Article
- β-Catenin regulates endocardial cushion growth by suppressing p21.Life science alliance · 2023Article
- Article
- Editorial: Heart valve diseases: from molecular mechanisms to clinical implications.Frontiers in molecular medicine · 2023Article
- TGF-β phospho antibody array identifies altered SMAD2, PI3K/AKT/SMAD, and RAC signaling contribute to the pathogenesis of myxomatous mitral valve disease.Frontiers in veterinary science · 2023Article
- Developmental dynamics of the neural crest-mesenchymal axis in creating the thymic microenvironment.Science advances · 2022Article
- First quantitative dosages: Strong correlations between non-5-HTFrontiers in cardiovascular medicine · 2022Article
- Profiling Genome-Wide DNA Methylation Patterns in Human Aortic and Mitral Valves.Frontiers in cardiovascular medicine · 2022Article
- DZIP1 regulates mammalian cardiac valve development through a Cby1-β-catenin mechanism.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Article
- Mitral Valve Prolapse and Its Motley Crew-Syndromic Prevalence, Pathophysiology, and Progression of a Common Heart Condition.Journal of the American Heart Association · 2021Article
- Metabolomics Analysis Reveals Deranged Energy Metabolism and Amino Acid Metabolic Reprogramming in Dogs With Myxomatous Mitral Valve Disease.Journal of the American Heart Association · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPathological processes underlying myxomatous mitral valve degeneration (MMVD) remain poorly understood. We sought to identify novel mechanisms contributing to the development of this condition. METHODS AND
resultsMicroarrays were used to measure gene expression in 11 myxomatous and 11 nonmyxomatous human mitral valves. Differential gene expression (thresholds P<0.05; fold-change >1.5) and pathway activation (Ingenuity) were confirmed using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Contributions of bone morphogenetic protein 4 and transforming growth factor (TGF)-β2 to differential gene expression were evaluated in vitro. Contributions of angiotensin II to differential pathway activation were examined in mice in vivo. A total of 2602 genes were differentially expressed between myxomatous and nonmyxomatous valves. Canonical TGF-β signaling was increased in MMVD because of increased ligand expression and derepression of SMA mothers against decapentaplegic 2/3 signaling and was confirmed with quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Myxomatous valves demonstrated activation of canonical bone morphogenetic protein and Wnt/β-catenin signaling and upregulation of their common target runt-related transcription factor 2. Our data set provided transcriptional and immunohistochemical evidence for activated immune cell infiltration. In vitro treatment of mitral valve interstitial cells with TGF-β2 increased β-catenin signaling at mRNA and protein levels, suggesting interactions between TGF-β2 and Wnt signaling. In vivo infusion of mice with angiotensin II recaptured several changes in signaling pathways characteristic of human MMVD.
conclusionsThese data support a new disease framework whereby activation of TGF-β2, bone morphogenetic protein 4, Wnt/β-catenin, or immune signaling plays major roles in the pathogenesis of MMVD. We propose these pathways act in a context-dependent manner to drive phenotypic changes that fundamentally differ from those observed in aortic valve disease and open novel avenues guiding future research into the pathogenesis 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.