ADAM10 controls the differentiation of the coronary arterial endothelium. Academic Article uri icon

Overview

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.

publication date

  • November 16, 2018

Research

keywords

  • ADAM10 Protein
  • Amyloid Precursor Protein Secretases
  • Cell Differentiation
  • Coronary Vessels
  • Endothelial Cells
  • Endothelium, Vascular
  • Membrane Proteins

Identity

PubMed Central ID

  • PMC6475616

Scopus Document Identifier

  • 85056704295

Digital Object Identifier (DOI)

  • 10.1007/s10456-018-9653-2

PubMed ID

  • 30446855

Additional Document Info

volume

  • 22

issue

  • 2