PXD012575

PXD012575 is an original dataset announced via ProteomeXchange.

Title	Endothelial EphB4 maintains vascular integrity and transport function in adult heart
Description	Dilated cardiomyopathy is a frequently occurring human disease compromising heart function and a major cause of cardiac death. The causes of cardiomyopathies are often unknown. There is increasing evidence indicating that endothelial cells lining blood vessels control the homeostasis of various organs, but the special properties and functional roles of the vasculature in the adult heart maintain remain little understood. Here, we have used mouse genetics, imaging and cell biology approaches to investigate how vascular homeostasis in the adult heart is controlled by EphB4 and its ligand ephrin-B2, which are known regulators of sprouting angiogenesis, vascular morphogenesis and arteriovenous differentiation during development. We show that inducible and endothelial cell-specific inactivation of the Ephb4 gene in adult mice is compatible with survival, but leads to rupturing of cardiac capillaries, cardiomyocyte hypertrophy, and pathological cardiac remodelling. In contrast, EphB4 is not required for the integrity and homeostatic function 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. Together, our findings establish that EphB4 maintains critical functional properties of the adult cardiac vasculature and thereby prevents dilated cardiomyopathy-like defects.
HostingRepository	PRIDE
AnnounceDate	2019-11-20
AnnouncementXML	Submission_2019-12-04_00:43:29.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hannes Drexler
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-31 05:05:50	ID requested
1	2019-11-20 04:50:04	announced
⏵ 2	2019-12-04 00:43:31	announced	2019-12-04: Updated publication reference for PubMed record(s): 31782728.

Lux, á, n G, Stewen J, D, í, az 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, Endothelial EphB4 maintains vascular integrity and transport function in adult heart. Elife, 8():(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: mouse, heart, endothelium, EPHB4, LC-MSMS, gene expression, metabolism

Hannes C. A. Drexler
contact affiliation	Max Planck Institut for Molecular Biomedicine Bioanalytical Mass Spectromentry Röntgenstr. 20 48149 Münster, Germany
contact email	hanes.drexler@mpi-muenster.mpg.de
lab head
Hannes Drexler
contact affiliation	Bioanalytical Mass Spectrometry
contact email	hannes.drexler@mpi-muenster.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012575
     1. Label: PRIDE project
     2. Name: Endothelial EphB4 maintains vascular integrity and transport function in adult heart