ArticleCardiovascular research2012
Developmental basis for filamin-A-associated myxomatous mitral valve disease.
Article in Cardiovascular research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis 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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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- The Role of Transforming Growth Factor-β Signaling in Myxomatous Mitral Valve Degeneration.Frontiers in cardiovascular medicine · 2022Pooled it
- SOX6 is expressed in various cell lineages in the developing mouse heart and contributes to proper valvuloseptal development.Anatomical record (Hoboken, N.J. : 2007) · 2026Article
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- Sertraline exposure during development may impact post-myocardial infarction survival in adult mice.Physiological reports · 2025Article
- Whole exome sequencing of 80 cases of sporadic mitral valve prolapse reveals novel disease-associated genes and variants in a Southern Chinese population.Genes & genomics · 2025Article
- Genetic variants of SLC6A4 and risk of coronary artery disease: insights from North Indian population.Orphanet journal of rare diseases · 2025Article
- New Insights on the Formation of the Mitral Valve Chordae Tendineae in Fetal Life.Journal of cardiovascular development and disease · 2024Article
- Differential Development of the Chordae Tendineae and Anterior Leaflet of the Bovine Mitral Valve.Journal of cardiovascular development and disease · 2024Article
- Valvulopathies and Genetics: Where are We?Reviews in cardiovascular medicine · 2024Review
- Epicardial deletion of Sox9 leads to myxomatous valve degeneration and identifies Cd109 as a novel gene associated with valve development.Journal of molecular and cellular cardiology · 2024Article
- Degenerative mitral regurgitation.Nature reviews. Disease primers · 2023Review
- The Potential of Intertwining Gene Diagnostics and Surgery for Mitral Valve Prolapse.Journal of clinical medicine · 2023Review
- Genetic mechanisms underlying arrhythmogenic mitral valve prolapse: Current and future perspectives.Heart rhythm O2 · 2023Review
- Genetics and pathophysiology of mitral valve prolapse.Frontiers in cardiovascular medicine · 2023Review
- Research Opportunities in the Treatment of Mitral Valve Prolapse: JACC Expert Panel.Journal of the American College of Cardiology · 2022Review
- DCHS1, Lix1L, and the Septin Cytoskeleton: Molecular and Developmental Etiology of Mitral Valve Prolapse.Journal of cardiovascular development and disease · 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
- Role of the Epicardium in the Development of the Atrioventricular Valves and Its Relevance to the Pathogenesis of Myxomatous Valve Disease.Journal of cardiovascular development and disease · 2021Review
- Macrophage lineages in heart valve development and disease.Cardiovascular research · 2021Review
Corrections and comments
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Authors and funding
20 authors at 12 institutions in 3 countries.
Funding
Abstract
aimsWe hypothesized that the structure and function of the mature valves is largely dependent upon how these tissues are built during development, and defects in how the valves are built can lead to the pathological progression of a disease phenotype. Thus, we sought to uncover potential developmental origins and mechanistic underpinnings causal to myxomatous mitral valve disease. We focus on how filamin-A, a cytoskeletal binding protein with strong links to human myxomatous valve disease, can function as a regulatory interface to control proper mitral valve development. METHODS AND
resultsFilamin-A-deficient mice exhibit abnormally enlarged mitral valves during foetal life, which progresses to a myxomatous phenotype by 2 months of age. Through expression studies, in silico modelling, 3D morphometry, biochemical studies, and 3D matrix assays, we demonstrate that the inception of the valve disease occurs during foetal life and can be attributed, in part, to a deficiency of interstitial cells to efficiently organize the extracellular matrix (ECM). This ECM organization during foetal valve gestation is due, in part, to molecular interactions between filamin-A, serotonin, and the cross-linking enzyme, transglutaminase-2 (TG2). Pharmacological and genetic perturbations that inhibit serotonin-TG2-filamin-A interactions lead to impaired ECM remodelling and engender progression to a myxomatous valve phenotype.
conclusionsThese findings illustrate a molecular mechanism by which valve interstitial cells, through a serotonin, TG, and filamin-A pathway, regulate matrix organization during foetal valve development. Additionally, these data indicate that disrupting key regulatory interactions during valve development can set the stage for the generation of postnatal myxomatous valve disease.
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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.