title: Myc regulates embryonic vascular permeability and remodeling.
abstract: Previous work has shown that c-Myc is required for adequate vasculogenesis and angiogenesis. To further investigate the contribution of Myc to these processes, we conditionally expressed c-Myc in embryonic endothelial cells using a tetracycline-regulated system. Endothelial Myc overexpression resulted in severe defects in the embryonic vascular system. Myc-expressing embryos undergo widespread edema formation and multiple hemorrhagic lesions. They die between embryonic days 14.5 and 17.5. The changes in vascular permeability are not caused by deficiencies in vascular basement membrane composition or pericyte coverage. However, the overall turnover of endothelial cells is elevated as is revealed by increased levels of both proliferation and apoptosis. Whole-mount immunohistochemical analysis revealed alterations in the architecture of capillary networks. The dermal vasculature of Myc-expressing embryos is characterized by a reduction in vessel branching, which occurs despite upregulation of the proangiogenic factors vascular endothelial growth factor-A and angiopoietin-2. Thus, the net outcome of an excess of vascular endothelial growth factor-A and angiopoietin-2 in the face of an elevated cellular turnover appears to be a defect in vascular integrity.
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Ulm, Germany.
authors.forename: Enikö
authors.initials: E
authors.lastname: Kokai
authors.forename: Florian
authors.initials: F
authors.lastname: Voss
authors.forename: Frank
authors.initials: F
authors.lastname: Fleischer
authors.forename: Sybille
authors.initials: S
authors.lastname: Kempe
authors.forename: Dragan
authors.initials: D
authors.lastname: Marinkovic
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.forename: Frank
authors.initials: F
authors.lastname: Leithäuser
authors.forename: Volker
authors.initials: V
authors.lastname: Schmidt
authors.forename: Urban
authors.initials: U
authors.lastname: Deutsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D042787:Receptor, TIE-2 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2