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
SURVEY AND SUMMARY VEGF-A mRNA processing, stability and translation: a paradigm for intricate regulation of gene expression at the post-transcriptional level
Eric Lacazette,Stefania Millevoi,Christian Touriol +2 more
- 01 Jan 2013
TL;DR: In this article, a review of the complex post-transcriptional regulatory switches that modulate the cellular VEGF-A level, a paradigmatic model of post-Transcriptional regulation is presented.
154
The angiopoietins and Tie2/Tek: adding to the complexity of cardiovascular development.
TL;DR: What is emerging from genetic, xenograft transplant, histochemical and cell culture experiments are that the response of endothelial cells to angiopoietins appears to be context and endothelial cell type specific.
154
Adipose Organ Development and Remodeling
TL;DR: The plastic properties of this organ could open new therapeutic perspectives in the obesity-related metabolic disease and in breast pathologies.
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Genetic and hypoxic regulation of angiogenesis in gliomas.
TL;DR: Understanding the contribution of genetic alterations and hypoxia in angiogenic dysregulation in astrocytic neoplasms will lead to the development of better anti-angiogenic therapies for this disease.
153
VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
Makoto Hayashi,Arindam Majumdar,Arindam Majumdar,Xiujuan Li,Jeremy Adler,Zuyue Sun,Simona Vertuani,Carina Hellberg,Sofie Mellberg,Sina Koch,Anna Dimberg,Gou Young Koh,Elisabetta Dejana,Heinz-Georg Belting,Markus Affolter,Gavin Thurston,Lars Holmgren,Dietmar Vestweber,Lena Claesson-Welsh +18 more
TL;DR: It is concluded that the role of Tie2 in maintenance of vascular quiescence involves VE-PTP-dependent dephosphorylation of VEGF receptor-2, and that VEGE-cadherin tyrosine phosphorylation, endothelial cell polarity and lumen formation is regulated.
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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