Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction, models CADASIL, and results in arteriovenous malformations

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Kofler , N M , Cuervo , H , Uh , M K , Murtomäki , A & Kitajewski , J 2015 , ' Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction, models CADASIL, and results in arteriovenous malformations ' , Scientific Reports , vol. 5 , 16449 . https://doi.org/10.1038/srep16449

Title: Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction, models CADASIL, and results in arteriovenous malformations
Author: Kofler, Natalie M.; Cuervo, Henar; Uh, Minji K.; Murtomäki, Aino; Kitajewski, Jan
Contributor: University of Helsinki, Biosciences
Date: 2015-11-13
Language: eng
Number of pages: 13
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/162425
Abstract: Pericytes regulate vessel stability and pericyte dysfunction contributes to retinopathies, stroke, and cancer. Here we define Notch as a key regulator of pericyte function during angiogenesis. In Notch1(+/-); Notch3(-/-) mice, combined deficiency of Notch1 and Notch3 altered pericyte interaction with the endothelium and reduced pericyte coverage of the retinal vasculature. Notch1 and Notch3 were shown to cooperate to promote proper vascular basement membrane formation and contribute to endothelial cell quiescence. Accordingly, loss of pericyte function due to Notch deficiency exacerbates endothelial cell activation caused by Notch1 haploinsufficiency. Mice mutant for Notch1 and Notch3 develop arteriovenous malformations and display hallmarks of the ischemic stroke disease CADASIL. Thus, Notch deficiency compromises pericyte function and contributes to vascular pathologies.
Subject: SMOOTH-MUSCLE-CELLS
AUTOSOMAL-DOMINANT ARTERIOPATHY
ENDOTHELIAL BASEMENT-MEMBRANE
CONDITION CAUSING STROKE
BLOOD-BRAIN-BARRIER
VASCULAR MORPHOGENESIS
SUBCORTICAL INFARCTS
SIGNALING PATHWAY
VESSEL INTEGRITY
MURAL CELLS
1184 Genetics, developmental biology, physiology
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