Journal ArticleDOI
Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
Peter Carmeliet,Valérie Ferreira,Georg Breier,Saskia Pollefeyt,Lena Kieckens,Marina Gertsenstein,Michaela Fahrig,Ann Vandenhoeck,Kendraprasad Harpal,Carmen Eberhardt,Cathérine Declercq,Judy Pawling,Lieve Moons,Desire Collen,Werner Risau,Andras Nagy,Andras Nagy +16 more
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TLDR
It is reported that formation of blood vessels was abnormal, but not abolished, in heterozygous VEGF-deficient (VEGF+/-) embryos, generated by aggregation of embryonic stem (ES) cells with tetraploid embryos (T-ES)16,17, and even more impaired in homozygous D1-VEGF- deficient (VDGF-/-) T-ES embryos, resulting in death at mid-gestation.Abstract:
The endothelial cell-specific vascular endothelial growth factor (VEGF) and its cellular receptors Flt-1 and Flk-1 have been implicated in the formation of the embryonic vasculature. This is suggested by their colocalized expression during embryogenesis and the impaired vessel formation in Flk-1 and Flt-1 deficient embryos. However, because Flt-1 also binds placental growth factor, a VEGF homologue, the precise role of VEGF was unknown. Here we report that formation of blood vessels was abnormal, but not abolished, in heterozygous VEGF-deficient (VEGF+/-) embryos, generated by aggregation of embryonic stem (ES) cells with tetraploid embryos (T-ES) and even more impaired in homozygous VEGF-deficient (VEGF-/-) T-ES embryos, resulting in death at mid-gestation. Similar phenotypes were observed in F1-VEGF+/- embryos, generated by germline transmission. We believe that this heterozygous lethal phenotype, which differs from the homozygous lethality in VEGF-receptor-deficient embryos, is unprecedented for a targeted autosomal gene inactivation, and is indicative of a tight dose-dependent regulation of embryonic vessel development by VEGF.read more
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Anatomy and development of the macula: specialisation and the vulnerability to macular degeneration INVITED REVIEW
TL;DR: In this article, the authors argue that at the macula stressed retinal neurons adapt during development to a limited blood supply from the choriocapillaris, which supplies little in excess of metabolic demand of the neural retina under normal conditions.
Journal ArticleDOI
Vascular Endothelial Growth Factor Is Increased in Patients With Preeclampsia
Michael J. Kupferminc,Yair Daniel,T E Englender,Amiram Bar-Am,Ariel Many,Ariel J. Jaffa,I. Gull,Joseph B. Lessing +7 more
TL;DR: This study was conducted to determine whether altered levels of vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of preeclampsia.
Journal ArticleDOI
Regulation of embryonic implantation.
TL;DR: The V EGF gene is one of the earliest genes activated during human preimplantation embryo development, giving rise to the assumption that VEGF is crucial for embryonic development, suggesting a role of this cytokine family during early embryonic development.
Journal ArticleDOI
Vascular Endothelial Growth Factor Gene Expression in Human Fetal Lung In Vitro
TL;DR: Data suggest that VEGF gene expression is regulated by both oxygen and cAMP in the developing human lung and localization of V EGF to the basement membrane of airway epithelial cells may be important for directing capillary development in the human lung.
Journal ArticleDOI
Neuroprotection of ischemic brain by vascular endothelial growth factor is critically dependent on proper dosage and may be compromised by angiogenesis.
Panya S. Manoonkitiwongsa,Robert L. Schultz,Douglas B. McCreery,Ernest F. Whitter,Patrick D. Lyden +4 more
TL;DR: It is suggested that in vivo neuroprotection of ischemic brains by exogenous VEGF does not necessarily occur simultaneously with angiogenesis, and neuroprotection may be greatly compromised by doses of V EGF capable of inducing angiogenic.
References
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Journal ArticleDOI
Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice.
Fouad Shalaby,Janet Rossant,Janet Rossant,Terry P. Yamaguchi,Terry P. Yamaguchi,Marina Gertsenstein,Xiang-Fu Wu,Xiang-Fu Wu,Martin L. Breitman,Martin L. Breitman,Andre C. Schuh +10 more
TL;DR: The generation of mice deficient in Flk-1 by disruption of the gene using homologous recombination in embryonic stem (ES) cells is reported, indicating that FlK-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo.
Journal Article
Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.
TL;DR: T tumors have "borrowed" fundamental mechanisms that developed in multicellular organisms for purposes of tissue defense, renewal, and repair and taught us something new about angiogenesis, namely, that vascular hyperpermeability and consequent plasma protein extravasation are important, perhaps essential, elements in its generation.
Journal ArticleDOI
Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium
Guo-Hua Fong,Janet Rossant,Janet Rossant,Marina Gertsenstein,Martin L. Breitman,Martin L. Breitman +5 more
TL;DR: It is reported that Flt-1 is essential for the organization of embryonic vasculature, but is not essential for endothelial cell differentiation, and it is suggested that the FlT-1 signalling pathway may regulate normal endothelium cell-cell or cell-matrix interactions during vascular development.
Journal ArticleDOI
Derivation of completely cell culture-derived mice from early-passage embryonic stem cells
TL;DR: Fully potent early passage R1 cells and the R1-S3 subclone should be very useful not only for ES cell-based genetic manipulations but also in defining optimal in vitro culture conditions for retaining the initial totipotency of ES cells.
Journal ArticleDOI
The fms-Like Tyrosine Kinase, a Receptor for Vascular Endothelial Growth Factor
TL;DR: Findings show that flt encodes a receptor for VEGF-VPF, a factor that induces vascular permeability when injected in the guinea pig skin and stimulates endothelial cell proliferation.