Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.
Napoleone Ferrara,Karen Carver-Moore,Helen Hsifei Chen,Mary Dowd,Lucy Lu,K. Sue O'Shea,Lyn Powell-Braxton,Kenneth J. Hillan,Mark W. Moore +8 more
TL;DR: The unexpected finding that loss of a single VEGF allele is lethal in the mouse embryo between days 11 and 12 was reported, and angiogenesis and blood-island formation were impaired, resulting in several developmental anomalies.
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Abstract: ANGIOGENESIS is required for a wide variety of physiological and pathological processes1. The endothelial cell-specific mitogen vascular endothelial growth factor (VEGF)2,3 is a major mediator of pathological angiogenesis4–6. Also, the expression of VEGF and its two receptors, Flt-1 and Flk-1/KDR, is related to the formation of blood vessels in mouse and rat embryos7–10. Mice homozygous for mutations that inactivate either receptor die in utero between days 8.5 and 9.5 (refs 11,12). However, ligand(s) other than VEGF might activate such receptors13,14. To assess the role of VEGF directly, we disrupted the VEGF gene in embryonic stem cells. Here we report the unexpected finding that loss of a single VEGF allele is lethal in the mouse embryo between days 11 and 12. Angiogenesis and blood-island formation were impaired, resulting in several developmental anomalies. Furthermore, VEGF-null embryonic stem cells exhibit a dramatically reduced ability to form tumours in nude mice.
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Citations
Role of vascular endothelial growth factor in diabetic vascular complications.
TL;DR: Improved understanding of the molecular mechanisms underlying these processes has permitted development of novel therapeutic interventions, several of which are now in human clinical trials, and various implications for the future care of vasculopathy associated with diabetes will be discussed.
304
Systemic and Ocular Safety of Intravitreal Anti-VEGF Therapies for Ocular Neovascular Disease
TL;DR: An overview of safety data for intravitreal anti-VEGF therapies, focusing primarily on randomized, controlled trials, is provided.
304
Utilization of Distinct Signaling Pathways by Receptors for Vascular Endothelial Cell Growth Factor and Other Mitogens in the Induction of Endothelial Cell Proliferation
Li Wha Wu,Lindsey D. Mayo,James D. Dunbar,Kelly M. Kessler,Melinda R. Baerwald,Eric A. Jaffe,Dongfang Wang,Robert S. Warren,David B. Donner +8 more
TL;DR: Two-hybrid cloning and immunoprecipitation from human umbilical vein endothelial cells (HUVEC) showed that KDR binds to and promotes the tyrosine phosphorylation of phospholipase Cγ (PLCγ), indicating that K DR is uniquely important to PLCγ activation in HUVEC.
301
Multiple developmental roles of vegf suggested by a lacz-tagged allele
Lucile Miquerol,Marina Gertsenstein,Kendraprasad Harpal,Janet Rossant,Janet Rossant,Andras Nagy,Andras Nagy +6 more
TL;DR: It is believed that the LacZ-tagged allele generated offers a precise means of detecting VEGF expression under a variety of physiological and pathological conditions.
301
Animal models of implantation.
Kevin Y. Lee,Francesco J. DeMayo +1 more
TL;DR: This review will discuss the differences in implantation between different animal models and describe how these differences can be utilized to investigate discrete implantation stages.
References
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.
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Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo
TL;DR: It is demonstrated that inhibition of the action of an angiogenic factor spontaneously produced by tumour cells may suppress tumour growth in vivo.
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Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders
Lloyd Paul Aiello,Robert L. Avery,Paul G. Arrigg,B A Keyt,Henry D. Jampel,Sweta Shah,Louis R. Pasquale,Hagen Thieme,Mami Iwamoto,John Edward Park +9 more
TL;DR: The data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.
3.8K
•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.
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