ArticleCardiovascular research2017
Loss of Axin2 results in impaired heart valve maturation and subsequent myxomatous valve disease.
Article in Cardiovascular research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- The Role of Transforming Growth Factor-β Signaling in Myxomatous Mitral Valve Degeneration.Frontiers in cardiovascular medicine · 2022Pooled it
- Novel mutations of AXIN2 identified in a Chinese Congenital Heart Disease Cohort.Journal of human genetics · 2019Trial
- Immune Mechanisms of Heart Valve Development, Homeostasis, and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Dysregulated TGFβ-ERK Signaling Drives Aberrant Extracellular Matrix Production in Noonan Syndrome-Associated Pulmonary Valve Stenosis.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- Integrin-mediated mTOR signaling drives TGF-β overactivity and myxomatous mitral valve degeneration in hypomorphic fibrillin-1 mice.The Journal of clinical investigation · 2025Article
- Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Mouse Congenital Myxomatous Valve Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Nkd1 functions downstream of Axin2 to attenuate Wnt signaling.Molecular biology of the cell · 2024Article
- Mendelian randomization reveals interactions of the blood proteome and immunome in mitral valve prolapse.Communications medicine · 2024Article
- Dynamic changes in mitral valve extracellular matrix, tissue mechanics and function in a mouse model of Marfan syndrome.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- The Potential of Intertwining Gene Diagnostics and Surgery for Mitral Valve Prolapse.Journal of clinical medicine · 2023Review
- β-Catenin regulates endocardial cushion growth by suppressing p21.Life science alliance · 2023Article
- Article
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- 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
- Genetics and pathophysiology of mitral valve prolapse.Frontiers in cardiovascular medicine · 2023Review
- Angiopoietin-like 2 is essential to aortic valve development in mice.Communications biology · 2022Article
- Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome.JACC. Basic to translational science · 2022Article
- Wnt Signaling in Heart Development and Regeneration.Current cardiology reports · 2022Review
- Tankyrase Inhibition Attenuates Cardiac Dilatation and Dysfunction in Ischemic Heart Failure.International journal of molecular sciences · 2022Article
Corrections and comments
- Commented on by
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
aimsMyxomatous valve disease (MVD) is the most common aetiology of primary mitral regurgitation. Recent studies suggest that defects in heart valve development can lead to heart valve disease in adults. Wnt/β-catenin signalling is active during heart valve development and has been reported in human MVD. The consequences of increased Wnt/β-catenin signalling due to Axin2 deficiency in postnatal valve remodelling and pathogenesis of MVD were determined. METHODS AND
resultsTo investigate the role of Wnt/β-catenin signalling, we analysed heart valves from mice deficient in Axin2 (KO), a negative regulator of Wnt/β-catenin signalling. Axin2 KO mice display enlarged mitral and aortic valves (AoV) after birth with increased Wnt/β-catenin signalling and cell proliferation, whereas Sox9 expression and collagen deposition are decreased. At 2 months in Axin2 KO mice, the valve extracellular matrix (ECM) is stratified but distal AoV leaflets remain thickened and develop aortic insufficiency. Progressive myxomatous degeneration is apparent at 4 months with extensive ECM remodelling and focal aggrecan-rich areas, along with increased BMP signalling. Infiltration of inflammatory cells is also observed in Axin2 KO AoV prior to ECM remodelling. Overall, these features are consistent with the progression of human MVD. Finally, Axin2 expression is decreased and Wnt/β-catenin signalling is increased in myxomatous mitral valves in a murine model of Marfan syndrome, supporting the importance of Wnt/β-catenin signalling in the development of MVD.
conclusionsAltogether, these data indicate that Axin2 limits Wnt/β-catenin signalling after birth and allows proper heart valve maturation. Moreover, dysregulation of Wnt/β-catenin signalling resulting from loss of Axin2 leads to progressive MVD.
Indexed as
Identifiers
What OpenQuestion holds
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.