ArticlePloS one2013
Nitric oxide synthase-3 promotes embryonic development of atrioventricular valves.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Manic Fringe promotes endothelial-to-mesenchymal transition mediated by the Notch signalling pathway during heart valve development.Journal of molecular medicine (Berlin, Germany) · 2025Article
- eNOS plays essential roles in the developing heart and aorta linked to disruption of Notch signalling.Disease models & mechanisms · 2024Article
- Standardisation and future of preclinical echocardiography.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Maternal nicotine exposure induces congenital heart defects in the offspring of mice.Journal of cellular and molecular medicine · 2022Article
- Crosstalk between nitric oxide and retinoic acid pathways is essential for amphioxus pharynx development.eLife · 2021Article
- Krox20 Regulates Endothelial Nitric Oxide Signaling in Aortic Valve Development and Disease.Journal of cardiovascular development and disease · 2019Article
- Is NO the Answer? The Nitric Oxide Pathway Can Support Bone Morphogenetic Protein 2 Mediated Signaling.Cells · 2019Article
- Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes.Antioxidants (Basel, Switzerland) · 2019Review
- Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes Mellitus in Mice.Journal of the American Heart Association · 2018Article
- Bicuspid aortic valve formation:Disease models & mechanisms · 2018Article
- Voluntary running exercise protects against sepsis-induced early inflammatory and pro-coagulant responses in aged mice.Critical care (London, England) · 2017Article
- Growth and maturation of heart valves leads to changes in endothelial cell distribution, impaired function, decreased metabolism and reduced cell proliferation.Journal of molecular and cellular cardiology · 2016Article
- Rac1 signaling is critical to cardiomyocyte polarity and embryonic heart development.Journal of the American Heart Association · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Nitric oxide synthase-3 (NOS3) has recently been shown to promote endothelial-to-mesenchymal transition (EndMT) in the developing atrioventricular (AV) canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT. To test this hypothesis, morphological and functional analysis of AV valves were performed in wild-type (WT) and NOS3(-/-) mice at postnatal day 0. Our data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3(-/-) compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3(-/-) mice. These phenotypes were all rescued by cardiac specific NOS3 overexpression. To assess EndMT, immunostaining of Snail1 was performed in the embryonic heart. Both total mesenchymal and Snail1(+) cells in the AV cushion were decreased in NOS3(-/-) compared with WT mice at E10.5 and E12.5, which was completely restored by cardiac specific NOS3 overexpression. In cultured embryonic hearts, NOS3 promoted transforming growth factor (TGFβ), bone morphogenetic protein (BMP2) and Snail1expression through cGMP. Furthermore, mesenchymal cell formation and migration from cultured AV cushion explants were decreased in the NOS3(-/-) compared with WT mice. We conclude that NOS3 promotes AV valve formation during embryonic heart development and deficiency in NOS3 results in AV valve insufficiency.
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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.