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(Circulation Research. 2009;104:1151.)
© 2009 American Heart Association, Inc.

Molecular Medicine

Myc Regulates Embryonic Vascular Permeability and Remodeling

Enikö Kokai, Florian Voss, Frank Fleischer, Sybille Kempe, Dragan Marinkovic, Hartwig Wolburg, Frank Leithäuser, Volker Schmidt, Urban Deutsch, Thomas Wirth

From the Institute of Physiological Chemistry (E.K., S.K., D.M., T.W.), Department of Pathology (F.L.), and Institute of Stochastics (F.V., F.F., V.S.), Ulm University, Germany; Institute of Pathology (H.W.), University of Tübingen Germany; and Theodor Kocher Institute (U.D.), University Bern, Switzerland.

Correspondence to Thomas Wirth, Physiological Chemistry, Albert-Einstein-Allee 11, Ulm 89081, Germany. E-mail thomas.wirth{at}uni-ulm.de

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.

Key Words: Myc • VEGF-A • vascular permeability • angiogenesis