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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A General Chemical Method to Regulate Protein Stability in the Mammalian Central Nervous System
TL;DR: A general technique in which the stability of a specific protein is regulated by a cell-permeable small molecule, and the ability of TMP to cross the blood-brain barrier enables the tunable regulation of proteins expressed in the mammalian central nervous system.
Journal ArticleDOI
Understanding the biology of angiogenesis: review of the most important molecular mechanisms.
TL;DR: Vascular endothelial growth factor-A is the most potent pro-angiogenic protein described to date and may reveal new targets for treating many diseases that are associated with this complex process.
Journal ArticleDOI
Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: Phase II study results
David R. Guyer,Gary E. Fish,Julia A. Haller,Allen C. Ho,Michael L. Klein,John I. Loewenstein,Daniel F. Martin,David H. Orth,Richard B Rosen,SR Sanislo,Steven D. Schwartz,Lawrence J. Singerman,George A. Williams +12 more
TL;DR: Anti-VEGF therapy is a promising treatment for various forms of ocular neovascularization, including AMD, and multiple intravitreal injections of the anti-VE GF aptamer were well tolerated in this phase II study.
Journal ArticleDOI
A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function
Frank J. Giordano,Hans-Peter Gerber,Simon-Peter Williams,Nicholas VanBruggen,Stuart Bunting,Pilar Ruiz-Lozano,Yusu Gu,Anjali K. Nath,Yan Huang,Reed Hickey,Nancy D. Dalton,Kirk L. Peterson,John Ross,Kenneth R. Chien,Napoleone Ferrara +14 more
TL;DR: These findings establish the critical importance of cardiac myocyte-derived vascular endothelial growth factor in cardiac morphogenesis and determination of heart function and establish an adult murine model of hypovascular nonnecrotic cardiac contractile dysfunction.
Journal ArticleDOI
Disruption of the Murine Calpain Small Subunit Gene, Capn4: Calpain Is Essential for Embryonic Development but Not for Cell Growth and Division
TL;DR: The physiological roles and possible functional distinctions of μ- and m-calpains remain unclear, but suggested functions include participation in cell division and migration, integrin-mediated signal transduction, apoptosis, and regulation of cellular control proteins such as cyclin D1 and p53.
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.