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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Selective Downregulation of VEGF-A 165 , VEGF-R 1 , and Decreased Capillary Density in Patients With Dilative but Not Ischemic Cardiomyopathy
Dietmar Abraham,Reinhold Hofbauer,Romana Schäfer,Roland Blumer,Patrick Paulus,Aurelia Miksovsky,Hannes Traxler,Alfred Kocher,Seyedhossein Aharinejad +8 more
TL;DR: Whether downregulation of certain VEGF isoforms in DCM is a cause or consequence of this disorder remains unclear, although upregulated V EGF levels in ICM are most likely the result of ischemia.
Journal ArticleDOI
Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy
TL;DR: The developmental processes required for placental vascularization and fetal follicular maturation are described and recent studies which show that estrogen has an important role in regulating these events are described.
Journal ArticleDOI
Pdgf mediates cardiac microvascular communication
Jay M. Edelberg,William C. Aird,Wei Wu,Helen Rayburn,Wilfred Mamuya,Mark Mercola,Robert D. Rosenberg +6 more
TL;DR: The studies suggest that environmental induction of PDGF-AB/alpha-receptor interaction is central to the regulation of cardiac microvascular endothelial cell hemostatic and angiogenic activity.
Journal ArticleDOI
Vascular Endothelial Growth Factor (VEGF)-Receptor2: Its Biological Functions, Major Signaling Pathway, and Specific Ligand VEGF-E
TL;DR: Interestingly, activation of VEGFR2 via V EGF-E in vivo results in a strong angiogenic response in mice, with minor effects on inflammation and hypervascular permeability compared with VEGF-A, suggesting that VEGf-E is a useful tool for proangiogenic therapy in ischemic diseases.
Journal ArticleDOI
Dental pulp stem cells in regenerative dentistry
TL;DR: The multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration, and fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry are discussed.
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.