ArticleCirculation2018
GATA6 Regulates Aortic Valve Remodeling, and Its Haploinsufficiency Leads to Right-Left Type Bicuspid Aortic Valve.
Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 96 citations in OpenAlex.
- Aortic valve disease: Novel animal models for advancing our understanding of the underlying mechanisms.Animal models and experimental medicine · 2026Review
- A cell atlas of the developing human outflow tract of the heart and its adult aortic valve derivatives.eLife · 2026Article
- Biomimetic Nanoparticles for Bone Regeneration: Construction Strategies and Therapeutic Mechanisms.International journal of nanomedicine · 2026Review
- Genetics of Congenital Heart Disease.Clinics in perinatology · 2025Review
- Zebrafish as a Versatile Model for Cardiovascular Research: Peering into the Heart of the Matter.Cells · 2025Review
- Navigating the Landscape of Translational Medicine of Calcific Aortic Valve Disease: Bridging Bench to Bedside.JACC. Asia · 2025Review
- Article
- Whole-Exome Sequencing Identifies Novel GATA5/6 Variants in Right-Sided Congenital Heart Defects.International journal of molecular sciences · 2025Article
- GATA6 regulates WNT and BMP programs to pattern precardiac mesoderm during the earliest stages of human cardiogenesis.bioRxiv : the preprint server for biology · 2025Article
- An animal model recapitulates human hepatic diseases associated withProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Deficient GATA6-CXCR7 signaling leads to bicuspid aortic valve.Disease models & mechanisms · 2024Article
- Gata6 functions in zebrafish endoderm to regulate late differentiating arterial pole cardiogenesis.Development (Cambridge, England) · 2024Article
- Intricate MIB1-NOTCH-GATA6 Interactions in Cardiac Valvular and Septal Development.Journal of cardiovascular development and disease · 2024Article
- Effect of deletion of the protein kinase PRKD1 on development of the mouse embryonic heart.Journal of anatomy · 2024Article
- Article
- Insights into the Inherited Basis of Valvular Heart Disease.Current cardiology reports · 2024Review
- Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024Review
- Novel pathogenic GATA6 variant associated with congenital heart disease, diabetes mellitus and necrotizing enterocolitis.Pediatric research · 2024Article
- Spatial transcriptomics reveals novel genes during the remodelling of the embryonic human arterial valves.PLoS genetics · 2023Article
- Implications of Bicuspid Aortic Valve Disease and Aortic Stenosis/Insufficiency as Risk Factors for Thoracic Aortic Aneurysm.Reviews in cardiovascular medicine · 2023Review
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12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBicuspid aortic valve (BAV), the most common congenital heart defect affecting 1% to 2% of the population, is a major risk factor for premature aortic valve disease and accounts for the majority of valve replacement. The genetic basis and mechanisms of BAV etiology and pathogenesis remain largely undefined.
methodsCardiac structure and function was assessed in mice lacking a Gata6 allele. Human GATA6 gene variants were analyzed in 452 BAV cases from the BAV consortium and 1849 controls from the Framingham GWAS (Genome Wide Association Study). GATA6 expression was determined in mice and human tissues using quantitative real-time polymerase chain reaction and immunohistochemistry. Mechanistic studies were carried out in cultured cells.
resultsGata6 heterozygous mice have highly penetrant right-left (RL)-type BAV, the most frequent type in humans. GATA6 transcript levels are lower in human BAV compared with normal tricuspid valves. Mechanistically, Gata6 haploinsufficiency disrupts valve remodeling and extracellular matrix composition through dysregulation of important signaling molecules, including matrix metalloproteinase 9. Cell-specific inactivation of Gata6 reveals an essential role for GATA6 in secondary heart field myocytes because loss of 1 Gata6 allele from Isl- 1-positive cells-but not from endothelial or neural crest cells-recapitulates the phenotype of Gata6 heterozygous mice.
conclusionsThe data identify a new cellular and molecular mechanism underlying BAV. The availability of an animal model for the most frequent human BAV opens the way for the elucidation of BAV pathogenesis and the development of much needed therapies.
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