Myc regulates embryonic vascular permeability and remodeling

Kokai, Enikö; Voss, Florian; Fleischer, Frank; Kempe, Sybille; Marinkovic, Dragan; Wolburg, Hartwig; Leithäuser, Frank; Schmidt, Volker; Deutsch, Urban; Wirth, Thomas (2009). Myc regulates embryonic vascular permeability and remodeling. Circulation research, 104(10), pp. 1151-9. Baltimore, Md.: Lippincott Williams & Wilkins 10.1161/CIRCRESAHA.108.191460

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Deutsch, Urban

ISSN:

0009-7330

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

05 Dec 2022 14:22

Publisher DOI:

10.1161/CIRCRESAHA.108.191460

PubMed ID:

19407242

Web of Science ID:

000266300600006

URI:

https://boris.unibe.ch/id/eprint/32153 (FactScience: 197081)

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