ArticleThe Journal of clinical investigation2004
TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 266 papers, 3 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
266 citing papers in PubMed, 3 syntheses or guidelines pooled it, 518 citations in OpenAlex.
- Skeletal muscle alterations in Marfan syndrome: a systematic review.Journal of muscle research and cell motility · 2025Pooled it
- Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse.European heart journal · 2022Pooled it
- The Role of Transforming Growth Factor-β Signaling in Myxomatous Mitral Valve Degeneration.Frontiers in cardiovascular medicine · 2022Pooled it
- Characteristics of mitral valve leaflet length in patients with pectus excavatum: A single center cross-sectional study.PloS one · 2019Trial
- Trial
- Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy.American heart journal · 2013Trial
- The aorta in Marfan syndrome: from molecular mechanisms to mechanobiological dysfunction.Cardiovascular research · 2026Review
- Lymphatic dysfunction and ZFP36 deficiency contribute to myxomatous valve degeneration in Marfan syndrome mice.The Journal of clinical investigation · 2026Article
- Lymphatic therapies open the valve in Marfan syndrome.The Journal of clinical investigation · 2026Article
- A Case of Myxoma-Like Degeneration in a Patient With Marfan Syndrome Mimicking Vegetation of Infective Endocarditis.Cureus · 2026Article
- Immune Mechanisms of Heart Valve Development, Homeostasis, and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Structural and Signaling Mechanisms of Aortic Wall Failure in Heritable Thoracic Aortic Disease.Cells · 2026Review
- Systematic Disruption of Zebrafish Fibrillin Genes Identifies a Translational Zebrafish Model for Marfan Syndrome.JACC. Basic to translational science · 2026Article
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- Mitral Annular Disjunction Associated with Ventricular Dilation in Pediatric Marfan Syndrome: A Cardiovascular Magnetic Resonance Study.Pediatric cardiology · 2025Article
- Atherosclerotic Plaque Instability and Rupture: Recommended Mouse Models to Empower Clinically Relevant Discoveries, Diagnostics, and Therapeutics.Arteriosclerosis, thrombosis, and vascular biology · 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
- Article
- Hemodynamic forces prevent myxomatous valve disease in mice through KLF2/4 signaling.The Journal of clinical investigation · 2025Article
- Characterization of LTBP2 mutation causing mitral valve prolapse.European heart journal open · 2025Article
206 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Mitral valve prolapse (MVP) is a common human phenotype, yet little is known about the pathogenesis of this condition. MVP can occur in the context of genetic syndromes, including Marfan syndrome (MFS), an autosomal-dominant connective tissue disorder caused by mutations in fibrillin-1. Fibrillin-1 contributes to the regulated activation of the cytokine TGF-beta, and enhanced signaling is a consequence of fibrillin-1 deficiency. We thus hypothesized that increased TGF-beta signaling may contribute to the multisystem pathogenesis of MFS, including the development of myxomatous changes of the atrioventricular valves. Mitral valves from fibrillin-1-deficient mice exhibited postnatally acquired alterations in architecture that correlated both temporally and spatially with increased cell proliferation, decreased apoptosis, and excess TGF-beta activation and signaling. In addition, TGF-beta antagonism in vivo rescued the valve phenotype, suggesting a cause and effect relationship. Expression analyses identified increased expression of numerous TGF-beta-related genes that regulate cell proliferation and survival and plausibly contribute to myxomatous valve disease. These studies validate a novel, genetically engineered murine model of myxomatous changes of the mitral valve and provide critical insight into the pathogenetic mechanism of such changes in MFS and perhaps more common nonsyndromic variants of mitral valve disease.
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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.