Myc Regulates Embryonic Vascular Permeability and Remodeling

2009
Authors
Kokai, EnikoeVoss, Florian
Fleischer, Frank
Kempe, Sybille
Marinković, Dragan

Wolburg, Hartwig
Leithaeuser, Frank
Schmidt, Volker
Deutsch, Urban

Wirth, Thomas
Article (Published version)

Metadata
Show full item recordAbstract
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 upregulatio...n 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. (Circ Res. 2009;104:1151-1159.)
Keywords:
Myc / VEGF-A / vascular permeability / angiogenesisSource:
Circulation Research, 2009, 104, 10, 1151-U59Publisher:
- Lippincott Williams & Wilkins, Philadelphia
Funding / projects:
- German Science FoundationGerman Research Foundation (DFG) [DFG-SFB451]
DOI: 10.1161/CIRCRESAHA.108.191460
ISSN: 0009-7330
PubMed: 19407242
WoS: 000266300600006
Scopus: 2-s2.0-66949134996
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rFASPERTY - JOUR AU - Kokai, Enikoe AU - Voss, Florian AU - Fleischer, Frank AU - Kempe, Sybille AU - Marinković, Dragan AU - Wolburg, Hartwig AU - Leithaeuser, Frank AU - Schmidt, Volker AU - Deutsch, Urban AU - Wirth, Thomas PY - 2009 UR - http://rfasper.fasper.bg.ac.rs/handle/123456789/252 AB - 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. (Circ Res. 2009;104:1151-1159.) PB - Lippincott Williams & Wilkins, Philadelphia T2 - Circulation Research T1 - Myc Regulates Embryonic Vascular Permeability and Remodeling EP - U59 IS - 10 SP - 1151 VL - 104 DO - 10.1161/CIRCRESAHA.108.191460 ER -
@article{ author = "Kokai, Enikoe and Voss, Florian and Fleischer, Frank and Kempe, Sybille and Marinković, Dragan and Wolburg, Hartwig and Leithaeuser, Frank and Schmidt, Volker and Deutsch, Urban and Wirth, Thomas", year = "2009", 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. (Circ Res. 2009;104:1151-1159.)", publisher = "Lippincott Williams & Wilkins, Philadelphia", journal = "Circulation Research", title = "Myc Regulates Embryonic Vascular Permeability and Remodeling", pages = "U59-1151", number = "10", volume = "104", doi = "10.1161/CIRCRESAHA.108.191460" }
Kokai, E., Voss, F., Fleischer, F., Kempe, S., Marinković, D., Wolburg, H., Leithaeuser, F., Schmidt, V., Deutsch, U.,& Wirth, T.. (2009). Myc Regulates Embryonic Vascular Permeability and Remodeling. in Circulation Research Lippincott Williams & Wilkins, Philadelphia., 104(10), 1151-U59. https://doi.org/10.1161/CIRCRESAHA.108.191460
Kokai E, Voss F, Fleischer F, Kempe S, Marinković D, Wolburg H, Leithaeuser F, Schmidt V, Deutsch U, Wirth T. Myc Regulates Embryonic Vascular Permeability and Remodeling. in Circulation Research. 2009;104(10):1151-U59. doi:10.1161/CIRCRESAHA.108.191460 .
Kokai, Enikoe, Voss, Florian, Fleischer, Frank, Kempe, Sybille, Marinković, Dragan, Wolburg, Hartwig, Leithaeuser, Frank, Schmidt, Volker, Deutsch, Urban, Wirth, Thomas, "Myc Regulates Embryonic Vascular Permeability and Remodeling" in Circulation Research, 104, no. 10 (2009):1151-U59, https://doi.org/10.1161/CIRCRESAHA.108.191460 . .