ArticleJournal of molecular and cellular cardiology2013
Endothelial nitric oxide signaling regulates Notch1 in aortic valve disease.
Article in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 106 papers.
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.
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Who cites it
106 citing papers in PubMed, 167 citations in OpenAlex.
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- Active endothelial and neural regulation of valve biology, health, and disease.Frontiers in cardiovascular medicine · 2026Review
- DAPT Mitigates Osteoarthritic Cartilage Degeneration and Enhances Articular Repair Through Targeted Modulation of the Gucy1a3 and Notch Signaling Axis.Drug design, development and therapy · 2026Article
- Orphan Nuclear Receptor NR4A1 Promotes Proliferation and Osteogenic Differentiation of Valvular Interstitial Cells through Activation of CCND2.International journal of biological sciences · 2026Article
- The Influence of Age on Notch1 and VEGF-A Responses During Exercise.Journal of aging research · 2026Article
- Modelling Tetralogy of Fallot: insights and limitations of animal models.Frontiers in cell and developmental biology · 2026Review
- Association of circulating Notch1 and VEGF with flow-mediated dilation and aerobic fitness in healthy adults.Translational exercise biomedicine · 2025Article
- Endothelial-mesenchymal crosstalk drives osteogenic differentiation of human osteoblasts through Notch signaling.Cell communication and signaling : CCS · 2025Article
- Communication between endothelial cells and osteoblasts in regulation of bone homeostasis: Notch players.Stem cell research & therapy · 2025Review
- Unveiling the intricacies of cardiac valve pathophysiology.Frontiers in cardiovascular medicine · 2025Review
- Single-cell analysis reveals the loss of FABP4-positive proliferating valvular endothelial cells relates to functional mitral regurgitation.BMC medicine · 2024Article
- Impact of genetic factors on antioxidant rescue of maternal diabetes-associated congenital heart disease.JCI insight · 2024Article
- S-Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte-Like Cells by Inhibiting Notch Signalling Pathway.Journal of cellular and molecular medicine · 2024Article
- Review
- Identification of congenital aortic valve malformations in juvenile natriuretic peptide receptor 2-deficient mice using high-frequency ultrasound.American journal of physiology. Heart and circulatory physiology · 2024Article
- Morusin Alleviates Aortic Valve Calcification by Inhibiting Valve Interstitial Cell Senescence Through Ccnd1/Trim25/Nrf2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Hippo Signaling Mediates TGFβ-Dependent Transcriptional Inputs in Cardiac Cushion Mesenchymal Cells to Regulate Extracellular Matrix Remodeling.Journal of cardiovascular development and disease · 2023Article
- Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead.International journal of molecular sciences · 2023Review
- Strategies for Development of Synthetic Heart Valve Tissue Engineering Scaffolds.Progress in materials science · 2023Article
- PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.Circulation research · 2023Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The mature aortic valve is composed of a structured trilaminar extracellular matrix that is interspersed with aortic valve interstitial cells (AVICs) and covered by endothelium. Dysfunction of the valvular endothelium initiates calcification of neighboring AVICs leading to calcific aortic valve disease (CAVD). The molecular mechanism by which endothelial cells communicate with AVICs and cause disease is not well understood. Using a co-culture assay, we show that endothelial cells secrete a signal to inhibit calcification of AVICs. Gain or loss of nitric oxide (NO) prevents or accelerates calcification of AVICs, respectively, suggesting that the endothelial cell-derived signal is NO. Overexpression of Notch1, which is genetically linked to human CAVD, retards the calcification of AVICs that occurs with NO inhibition. In AVICs, NO regulates the expression of Hey1, a downstream target of Notch1, and alters nuclear localization of Notch1 intracellular domain. Finally, Notch1 and NOS3 (endothelial NO synthase) display an in vivo genetic interaction critical for proper valve morphogenesis and the development of aortic valve disease. Our data suggests that endothelial cell-derived NO is a regulator of Notch1 signaling in AVICs in the development of the aortic valve and adult aortic 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.