Format

Send to

Choose Destination
Elife. 2019 Nov 29;8. pii: e45863. doi: 10.7554/eLife.45863.

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

Author information

1
Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
2
Regulatory Genomics Laboratory, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
3
Department of Clinical Radiology, University Hospital Münster, Münster, Germany.
4
Bioanalytical Mass Spectrometry Unit, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
5
Electron Microscopy Unit, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
6
Institute for Physiology II, University of Münster, Münster, Germany.
7
European Institute for Molecular Imaging, University of Münster, Münster, Germany.
8
Discovery Biology, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
9
Faculty of Medicine, University of Münster, Münster, Germany.
#
Contributed equally

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.

KEYWORDS:

blood vessel; cardiomyocyte; developmental biology; endothelial cell; heart; homeostasis; mouse

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center