Deletion of Adam10 in endothelial cells leads to defects in organ-specific vascular structures Journal Article

   

Authors:	Glomski, K.; Monette, S.; Manova, K.; De Strooper, B.; Saftig, P.; Blobel, C. P.
Article Title:	Deletion of Adam10 in endothelial cells leads to defects in organ-specific vascular structures
Abstract:	During vertebrate angiogenesis, Notch regulates the cell-fate decision between vascular tip cells versus stalk cells. Canonical Notch signaling depends on sequential proteolytic events, whereby interaction of Notch with membrane-anchored ligands triggers proteolytic processing, first by Adam10 and then presenilins. This liberates the Notch intracellular domain, allowing it to enter the nucleus and activate Notch-dependent genes. Here we report that conditional inactivation of Adam10 in endothelial cells (A10ΔEC) recapitulates the increased branching and density of the retinal vasculature that is also caused by interfering with Notch signaling. Moreover, A10ΔEC mice have additional vascular abnormalities, including aberrant subcapsular hepatic veins, enlarged glomeruli, intestinal polyps containing endothelial cell masses, abnormal endochondral ossification, leading to stunted long bone growth and increased pathologic neovascularization following oxygen-induced retinopathy. Our findings support a model in which Adam10 is a crucial regulator of endothelial cell-fate decisions, most likely because of its essential role in canonical Notch signaling. © 2011 by The American Society of Hematology.
Keywords:	signal transduction; gene deletion; nonhuman; erythropoiesis; protein; notch receptor; cell fate; embryo development; creatinine; creatinine blood level; urea nitrogen blood level; alanine aminotransferase blood level; aspartate aminotransferase blood level; gamma glutamyl transferase blood level; endothelium cell; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; albumin; retinopathy; gene inactivation; cholesterol; cholesterol blood level; alkaline phosphatase blood level; gamma glutamyltransferase; sodium; neovascularization (pathology); vascular disease; potassium; hematology; intestine polyp; albumin blood level; bone growth; globulin; adam10 endopeptidase; enchondral ossification; hepatic vein; long bone; retina blood vessel
Journal Title:	Blood
Volume:	118
Issue:	4
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	2011-07-28
Start Page:	1163
End Page:	1174
Language:	English
DOI:	10.1182/blood-2011-04-348557
PROVIDER:	scopus
PMCID:	PMC3148163
PUBMED:	21652679
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-79961009646&partnerID=40&md5=78898b2995ba131a5f02ce7625a4ec55
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 3 October 2011" - "CODEN: BLOOA" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/12981