ArticleDevelopment (Cambridge, England)2013
UBIAD1-mediated vitamin K2 synthesis is required for vascular endothelial cell survival and development.
Article in Development (Cambridge, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 57 citations in OpenAlex.
- GlialeLife · 2026Article
- myh9b is a critical non-muscle myosin II encoding gene that interacts with myh9a and myh10 during zebrafish development in both compensatory and redundant pathways.G3 (Bethesda, Md.) · 2025Article
- Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation.GeroScience · 2024Article
- Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation.The FEBS journal · 2022Article
- Animal Models of Coenzyme Q Deficiency: Mechanistic and Translational Learnings.Antioxidants (Basel, Switzerland) · 2021Review
- Article
- Construction of a novel MK-4 biosynthetic pathway in Pichia pastoris through heterologous expression of HsUBIAD1.Microbial cell factories · 2019Article
- Effects of combined menaquinone-4 and PTHEndocrine · 2019Article
- Clinical diversity in patients with Schnyder corneal dystrophy-a novel and known UBIAD1 pathogenic variants.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2018Article
- Methods for Structural and Functional Analyses of Intramembrane Prenyltransferases in the UbiA Superfamily.Methods in enzymology · 2017Article
- Protective effect of VK2 on glucocorticoid-treated MC3T3-E1 cells.International journal of molecular medicine · 2017Article
- Tissue Concentrations of Vitamin K and Expression of Key Enzymes of Vitamin K Metabolism Are Influenced by Sex and Diet but Not Housing in C57Bl6 Mice.The Journal of nutrition · 2016Article
- Bringing Bioactive Compounds into Membranes: The UbiA Superfamily of Intramembrane Aromatic Prenyltransferases.Trends in biochemical sciences · 2016Review
- Vitamin K2 Ameliorates Damage of Blood Vessels by Glucocorticoid: a Potential Mechanism for Its Protective Effects in Glucocorticoid-induced Osteonecrosis of the Femoral Head in a Rat Model.International journal of biological sciences · 2016Article
- Vitamin K2 Prevents Glucocorticoid-induced Osteonecrosis of the Femoral Head in Rats.International journal of biological sciences · 2016Article
- Vitamin K and hepatocellular carcinoma: The basic and clinic.World journal of clinical cases · 2015Review
- Polo-like kinase 2 regulates angiogenic sprouting and blood vessel development.Developmental biology · 2015Article
- Review
- Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction.Nature genetics · 2015Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Multi-organ animals, such as vertebrates, require the development of a closed vascular system to ensure the delivery of nutrients to, and the transport of waste from, their organs. As a result, an organized vascular network that is optimal for tissue perfusion is created through not only the generation of new blood vessels but also the remodeling and maintenance of endothelial cells via apoptotic and cell survival pathways. Here, we show that UBIAD1, a vitamin K2/menaquinone-4 biosynthetic enzyme, functions cell-autonomously to regulate endothelial cell survival and maintain vascular homeostasis. From a recent vascular transgene-assisted zebrafish forward genetic screen, we have identified a ubiad1 mutant, reddish/reh, which exhibits cardiac edema as well as cranial hemorrhages and vascular degeneration owing to defects in endothelial cell survival. These findings are further bolstered by the expression of UBIAD1 in human umbilical vein endothelial cells and human heart tissue, as well as the rescue of the reh cardiac and vascular phenotypes with either zebrafish or human UBIAD1. Furthermore, we have discovered that vitamin K2, which is synthesized by UBIAD1, can also rescue the reh vascular phenotype but not the reh cardiac phenotype. Additionally, warfarin-treated zebrafish, which have decreased active vitamin K, display similar vascular degeneration as reh mutants, but exhibit normal cardiac function. Overall, these findings reveal an essential role for UBIAD1-generated vitamin K2 to maintain endothelial cell survival and overall vascular homeostasis; however, an alternative UBIAD1/vitamin K-independent pathway may regulate cardiac function.
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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.