ELTD1 is present in extracellular vesicles derived from endothelial cells as a cleaved extracellular domain which induces in vivo angiogenesis

ELTD1/ADGRL4 is an adhesion GPCR with an important role in angiogenesis. We recently identified a role for ELTD1 in wound repair and inflammation. Activation of ELTD1 in endothelial cells results in a type II EMT to myofibroblast‐like cells that have enhanced angiogenic ability. Furthermore, express...

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Published in:Journal of extracellular biology Vol. 1; no. 8; pp. e52 - n/a
Main Authors: Sheldon, Helen, Zhang, Wei, Bridges, Esther, Ang, Koon Hwee, Lin, Salwa, Masiero, Massimo, Li, Demin, Handford, Penny A., Whiteman, Pat, Fischer, Roman, Buffa, Francesca, Vatish, Manu, Banham, Alison H., Harris, Adrian L.
Format: Journal Article
Language:English
Published: United States John Wiley & Sons, Inc 01.08.2022
John Wiley and Sons Inc
Wiley
Subjects:
Angiogenesis
Antibodies
Biomarkers
Cell activation
Cell size
Cells
Cloning
ELTD1
Endothelial cells
Endothelium
Epidermal growth factor
Extracellular vesicles
Flow cytometry
G protein-coupled receptors
Immune response
Inflammation
Manufacturers
Mass spectroscopy
Microenvironments
migrasomes
Pre-eclampsia
Proteins
Proteomics
Wound healing
United Kingdom > UK
Fiji
migrasomes
ELTD1
extracellular vesicles
angiogenesis
ISSN:2768-2811, 2768-2811
Online Access:Get full text
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Summary:ELTD1/ADGRL4 is an adhesion GPCR with an important role in angiogenesis. We recently identified a role for ELTD1 in wound repair and inflammation. Activation of ELTD1 in endothelial cells results in a type II EMT to myofibroblast‐like cells that have enhanced angiogenic ability. Furthermore, expression of Eltd1 in murine breast cancer cells increases tumour growth by increasing blood vessel size and perfusion and by creating an immunosuppressive microenvironment. As extracellular vesicles (EVs) are known to be involved in vascular development, growth and maturation we investigated the composition and functional effects of the EVs isolated from ELTD1 expressing cells to elucidate their role in these processes. A highly glycosylated form of the extracellular domain (ECD) of ELTD1 is readily incorporated into EVs. Using mass spectrometry‐based proteomics we identified proteins that are enriched in ELTD1‐EVs and are involved in haemostasis and immune responses. ELTD1 enriched EVs were pro‐angiogenic in vivo and in vitro and the presence of the ECD alone induced endothelial sprouting. In endothelial cells experiencing laminar flow, ELTD1 levels were reduced in the EVs when they are quiescent, showing a relationship between ELTD1 and the activation state of the endothelium. Using FACS, we detected a significant increase in vesicular ELTD1 in the plasma of patients with preeclampsia, a condition characterized by endothelial dysfunction. These data confirm a role for ELTD1 in wound repair and inflammation and reveal its potential as a biomarker of vessel dysfunction.
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ISSN:2768-2811
2768-2811
DOI:10.1002/jex2.52