Kofler, Natalie MCuervo, HenarUh, Minji KMurtomäki, AinoKitajewski, Jan2024-01-172024-01-172015-11-13Sci Rep. 2015 Nov 13:5:16449.http://hdl.handle.net/20.500.12105/17218Pericytes 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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/AnimalsArteriovenous MalformationsBlotting, WesternCADASILCell DifferentiationCells, CulturedDisease Models, AnimalEndothelial CellsGene ExpressionHEK293 CellsHumansMatrix Metalloproteinase 2Mice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalMicroscopy, Electron, TransmissionMuscle, Smooth, VascularPericytesReceptor, Notch1Receptor, Notch3Receptor, Platelet-Derived Growth Factor betaReceptors, NotchRetinal VesselsReverse Transcriptase Polymerase Chain ReactionTime FactorsAttribution-NonCommercial-NoDerivatives 4.0 Internacional2656357051644910.1038/srep164492045-2322Scientific reportsopen access