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
c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression
Troy A. Baudino,Catriona McKay,Helene Pendeville-Samain,Jonas Nilsson,Kirsteen H. Maclean,Elsie White,Ann C. Davis,James N. Ihle,John L. Cleveland +8 more
TL;DR: Findings support the model wherein c-Myc promotes cell growth and transformation, as well as vascular and hematopoietic development, by functioning as a master regulator of angiogenic factors.
Vascular endothelial growth factor: Crystal structure and functional mapping of the kinase domain receptor binding site
Yves A. Muller,Bing Li,H.W. Christinger,James A. Wells,Brian C. Cunningham,Abraham M. de Vos +5 more
TL;DR: Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended, and functional analysis of the binding epitopes for two receptor-blocking antibodies reveal different binding determinants near each of the KDR binding hot spots.
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Angiopoietins 3 and 4: Diverging gene counterparts in mice and humans
David M. Valenzuela,Jennifer A. Griffiths,Rojas Jose F,Aldrich Thomas H,Pamela F. Jones,Hao Zhou,Joyce McClain,Neal G. Copeland,Debra J. Gilbert,Nancy A. Jenkins,Tammy T. Huang,Nick Papadopoulos,Maisonpierre Peter C,Samuel Davis,George D. Yancopoulos +14 more
TL;DR: The angiopoietins have recently joined the members of the vascular endothelial growth factor family as the only known growth factors largely specific for vascular endothelium as discussed by the authors, and they include a naturally occurring agonist, angioietin-1, as well as an naturally occurring antagonist, angiopooietin2, both of which act by means of the Tie2 receptor.
509
Angiogenesis in the Placenta
TL;DR: Regulators of angiogenesis that are currently being developed may provide novel and powerful methods to ensure positive outcomes for most pregnancies.
509
Vascular Endothelial Growth Factor Gene Therapy Increases Survival, Promotes Lung Angiogenesis, and Prevents Alveolar Damage in Hyperoxia-Induced Lung Injury Evidence That Angiogenesis Participates in Alveolarization
Bernard Thébaud,Faruqa Ladha,Evangelos D. Michelakis,Monika Sawicka,Gavin Thurston,Farah Eaton,Kyoko Hashimoto,Gwyneth Harry,Alois Haromy,Greg Korbutt,Stephen L. Archer +10 more
TL;DR: These findings underscore the importance of the vasculature in what is traditionally thought of as an airway disease and open new therapeutic avenues for lung diseases characterized by irreversible loss of alveoli through the modulation of angiogenic growth factors.
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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.
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•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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