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ADAM10 controls the differentiation of the coronary arterial endothelium.

TitleADAM10 controls the differentiation of the coronary arterial endothelium.
Publication TypeJournal Article
Year of Publication2018
AuthorsFarber, G, Parks, MM, Guahmich, NLustgarten, Zhang, Y, Monette, S, Blanchard, SC, Di Lorenzo, A, Blobel, CP
JournalAngiogenesis
Date Published2018 Nov 16
ISSN1573-7209
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.

DOI10.1007/s10456-018-9653-2
Alternate JournalAngiogenesis
PubMed ID30446855
Grant ListR01 GM064750 / GM / NIGMS NIH HHS / United States
R21 NS104512 / NS / NINDS NIH HHS / United States
17PRE33380001 / / American Heart Association /
CA008748 / / National Cancer Institute /
GM64750 / / National Institute of General Medical Sciences /