ArticleJournal of the American Heart Association2016
Endothelial Notch1 Is Required for Proper Development of the Semilunar Valves and Cardiac Outflow Tract.
Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Single-cell reconstruction and mutation enrichment analysis identifies dysregulated cardiomyocyte and endothelial cells in congenital heart disease.Physiological genomics · 2023Pooled it
- Cardiac Organoids for Modeling Congenital Heart Disease: From Genetic Discovery to Therapeutic Screening.Current cardiology reports · 2026Review
- Coronary endothelial cells receive Notch1 signal during heart development.Biochemistry and biophysics reports · 2026Article
- Modelling Tetralogy of Fallot: insights and limitations of animal models.Frontiers in cell and developmental biology · 2026Review
- Uncovering Developmental Origins of Aortic Valve Disease: A Clinically Relevant Genetic Model of Aortic Stenosis.JACC. Basic to translational science · 2025Article
- Bicuspid Aortic Valve and Sudden Cardiac Death.Life (Basel, Switzerland) · 2025Review
- Navigating the Landscape of Translational Medicine of Calcific Aortic Valve Disease: Bridging Bench to Bedside.JACC. Asia · 2025Review
- Artificial intelligence-assisted organoid construction in congenital heart disease: current applications and future prospects.Frontiers in bioengineering and biotechnology · 2025Review
- Maternal Blood Group Is a Possible Predictor for Developing Congenital Heart Disease in Turkish Children with Down's Syndrome.Journal of pediatric genetics · 2024Article
- Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead.International journal of molecular sciences · 2023Review
- Effect of maternal pregestational diabetes mellitus on congenital heart diseases.World journal of pediatrics : WJP · 2023Review
- Evaluating High-Confidence Genes in Conotruncal Cardiac Defects by Gene Burden Analyses.Journal of the American Heart Association · 2023Article
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- Congenital aortic valve stenosis: from pathophysiology to molecular genetics and the need for novel therapeutics.Frontiers in cardiovascular medicine · 2023Review
- Capturing heart valve development with Gene Ontology.Frontiers in genetics · 2023Article
- Angiopoietin-like 2 is essential to aortic valve development in mice.Communications biology · 2022Article
- Bicuspid Aortic Valve and Premature Ventricular Beats in Athletes.International journal of environmental research and public health · 2022Article
- Prevalence of Genetic Diagnoses in a Cohort With Valvar Pulmonary Stenosis.Circulation. Genomic and precision medicine · 2022Article
- Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.International journal of molecular sciences · 2022Review
- Single-cell RNA-sequencing analysis of aortic valve interstitial cells demonstrates the regulation of integrin signaling by nitric oxide.Frontiers in cardiovascular medicine · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundCongenital heart disease is the most common type of birth defect, affecting ≈2% of the population. Malformations involving the cardiac outflow tract and semilunar valves account for >50% of these cases predominantly because of a bicuspid aortic valve, which has an estimated prevalence of 1% in the population. We previously reported that mutations in NOTCH1 were a cause of bicuspid aortic valve in nonsyndromic autosomal-dominant human pedigrees. Subsequently, we described a highly penetrant mouse model of aortic valve disease, consisting of a bicuspid aortic valve with thickened cusps and associated stenosis and regurgitation, in Notch1-haploinsufficient adult mice backcrossed into a Nos3-null background. METHODS AND
resultsHere, we described the congenital cardiac abnormalities in Notch1(+/-);Nos3(-/-) embryos that led to ≈65% lethality by postnatal day 10. Although expected Mendelian ratios of Notch1(+/-);Nos3(-/-) embryos were found at embryonic day 18.5, histological examination revealed thickened, malformed semilunar valve leaflets accompanied by additional anomalies of the cardiac outflow tract including ventricular septal defects and overriding aorta. The aortic valve leaflets of Notch1(+/-);Nos3(-/-) embryos at embryonic day 15.5 were significantly thicker than controls, consistent with a defect in remodeling of the semilunar valve cushions. In addition, we generated mice haploinsufficient for Notch1 specifically in endothelial and endothelial-derived cells in a Nos3-null background and found that Notch1(fl/+);Tie2-Cre(+/-);Nos3(-/-) mice recapitulate the congenital cardiac phenotype of Notch1(+/-);Nos3(-/-) embryos.
conclusionsOur data demonstrate the role of endothelial Notch1 in the proper development of the semilunar valves and cardiac outflow tract.
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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.