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EndothelialCell–Specific FGD5Involvement inVascular PruningDefines NeovesselFate in Mice Caroline ChengRemco HaasdijkDennie Tempel2012 год

Endothelial Cell–Specific FGD5 Involvement in Vascular Pruning Defines Neovessel Fate in Mice
статья из журнала

Страница публикацииПубликация в OpenAlex
Аннотация: Background— New vessel formation contributes to organ development during embryogenesis and tissue repair in response to mechanical damage, inflammation, and ischemia in adult organisms. Early angiogenesis includes formation of an excessive primitive network that needs to be reorganized into a secondary vascular network with higher hierarchical structure. Vascular pruning, the removal of aberrant neovessels by apoptosis, is a vital step in this process. Although multiple molecular pathways for early angiogenesis have been identified, little is known about the genetic regulators of secondary network development. Methods and Results— Using a transcriptomics approach, we identified a new endothelial specific gene named FYVE, RhoGEF, and PH domain–containing 5 (FGD5) that plays a crucial role in vascular pruning. Loss- and gain-of-function studies demonstrate that FGD5 inhibits neovascularization, indicated by in vitro tube-formation, aortic-ring, and coated-bead assays and by in vivo coated-bead plug assays and studies in the murine retina model. FGD5 promotes apoptosis-induced vaso-obliteration via induction of the hey1-p53 pathway by direct binding and activation of cdc42. Indeed, FGD5 correlates with apoptosis in endothelial cells during vascular remodeling and was linked to rising p21 CIP1 levels in aging mice. Conclusion— We have identified FGD5 as a novel genetic regulator of vascular pruning by activation of endothelial cell–targeted apoptosis.
Год издания: 2012
Авторы: Caroline Cheng, Remco Haasdijk, Dennie Tempel, Esther H. M. van de Kamp, Robert Herpers, Frank L. Bos, Wijnand K. den Dekker, Lau A.J. Blonden, Renate de Jong, Petra E. Bürgisser, Ihsan Chrifi, Erik A.L. Biessen, Stefanie Dimmeler, Stefan Schulte‐Merker, Henricus J. Duckers
Издательство: Lippincott Williams & Wilkins
Источник: Circulation
Ключевые слова: Angiogenesis and VEGF in Cancer, Kruppel-like factors research, Protease and Inhibitor Mechanisms
Другие ссылки: Circulation (HTML)
PubMed (HTML)