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Apelin signaling drives vascular endothelial cells towards a pro-angiogenic state

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Item Type:Article
Title:Apelin signaling drives vascular endothelial cells towards a pro-angiogenic state
Creators Name:Helker, C.S.M. and Eberlein, J. and Wilhelm, K. and Sugino, T. and Malchow, J. and Schuermann, A. and Baumeister, S. and Kwon, H.B. and Maischein, H.M. and Potente, M. and Herzog, W. and Stainier, D.Y.R.
Abstract:To form new blood vessels (angiogenesis), endothelial cells (ECs) must be activated and acquire highly migratory and proliferative phenotypes. However, the molecular mechanisms that govern these processes are incompletely understood. Here, we show that Apelin signaling functions to drive ECs into such an angiogenic state. Zebrafish lacking Apelin signaling exhibit defects in endothelial tip cell morphology and sprouting. Using transplantation experiments, we find that in mosaic vessels, wild-type ECs leave the dorsal aorta (DA) and form new vessels while neighboring ECs defective in Apelin signaling remain in the DA. Mechanistically, Apelin signaling enhances glycolytic activity in ECs at least in part by increasing levels of the growth-promoting transcription factor c-Myc. Moreover, Apelin expression is regulated by Notch signaling, and its function is required for the hypersprouting phenotype in Delta-like 4 (Dll4) knockdown embryos. These data provide new insights into fundamental principles of blood vessel formation and Apelin signaling, enabling a better understanding of vascular growth in health and disease.
Keywords:Blood Vessels, Chemokines, Endothelial Cells, Morphogenesis, Signal Transduction, Zebrafish Proteins, Animals, Zebrafish
Publisher:eLife Sciences Publications
Page Range:e55589
Date:21 September 2020
Official Publication:https://doi.org/10.7554/eLife.55589
PubMed:View item in PubMed

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