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01-05-2019 | Original Paper

ADAM10 controls the differentiation of the coronary arterial endothelium

Authors: Gregory Farber, Matthew M. Parks, Nicole Lustgarten Guahmich, Yi Zhang, Sébastien Monette, Scott C. Blanchard, Annarita Di Lorenzo, Carl P. Blobel

Published in: Angiogenesis | Issue 2/2019

Abstract

The coronary vasculature is crucial for normal heart function, yet much remains to be learned about its development, especially the maturation of coronary arterial endothelium. Here, we show that endothelial inactivation of ADAM10, a key regulator of Notch signaling, leads to defects in coronary arterial differentiation, as evidenced by dysregulated genes related to Notch signaling and arterial identity. Moreover, transcriptome analysis indicated reduced EGFR signaling in A10ΔEC coronary endothelium. Further analysis revealed that A10ΔEC mice have enlarged dysfunctional hearts with abnormal myocardial compaction, and increased expression of venous and immature endothelium markers. These findings provide the first evidence for a potential role for endothelial ADAM10 in cardioprotective homeostatic EGFR signaling and implicate ADAM10/Notch signaling in coronary arterial cell specification, which is vital for normal heart development and function. The ADAM10/Notch signaling pathway thus emerges as a potential therapeutic target for improving the regenerative capacity and maturation of the coronary vasculature.

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Title: ADAM10 controls the differentiation of the coronary arterial endothelium
Authors: Gregory Farber
Matthew M. Parks
Nicole Lustgarten Guahmich
Yi Zhang
Sébastien Monette
Scott C. Blanchard
Annarita Di Lorenzo
Carl P. Blobel
Publication date: 01-05-2019
Publisher: Springer Netherlands
Published in: Angiogenesis / Issue 2/2019
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-018-9653-2

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