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Endothelial EphB4 maintains vascular integrity and transport function in adult heart.

Authors :
Luxán G
Stewen J
Díaz N
Kato K
Maney SK
Aravamudhan A
Berkenfeld F
Nagelmann N
Drexler HC
Zeuschner D
Faber C
Schillers H
Hermann S
Wiseman J
Vaquerizas JM
Pitulescu ME
Adams RH
Source :
ELife [Elife] 2019 Nov 29; Vol. 8. Date of Electronic Publication: 2019 Nov 29.
Publication Year :
2019

Abstract

The homeostasis of heart and other organs relies on the appropriate provision of nutrients and functional specialization of the local vasculature. Here, we have used mouse genetics, imaging and cell biology approaches to investigate how homeostasis in the adult heart is controlled by endothelial EphB4 and its ligand ephrin-B2, which are known regulators of vascular morphogenesis and arteriovenous differentiation during development. We show that inducible and endothelial cell-specific inactivation of Ephb4 in adult mice is compatible with survival, but leads to rupturing of cardiac capillaries, cardiomyocyte hypertrophy, and pathological cardiac remodeling. In contrast, EphB4 is not required for integrity and homeostasis of capillaries in skeletal muscle. Our analysis of mutant mice and cultured endothelial cells shows that EphB4 controls the function of caveolae, cell-cell adhesion under mechanical stress and lipid transport. We propose that EphB4 maintains critical functional properties of the adult cardiac vasculature and thereby prevents dilated cardiomyopathy-like defects.<br />Competing Interests: GL, JS, ND, KK, SM, AA, FB, NN, HD, DZ, CF, HS, SH, JV, MP, RA No competing interests declared, JW is affiliated with AstraZeneca. The author has no financial interests to declare.<br /> (© 2019, Luxán et al.)

Details

Language :
English
ISSN :
2050-084X
Volume :
8
Database :
MEDLINE
Journal :
ELife
Publication Type :
Academic Journal
Accession number :
31782728
Full Text :
https://doi.org/10.7554/eLife.45863