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- W1489220260 abstract "During angiogenesis, nascent blood vessels sprout frompre-existing vasculature and recruit pericytes to induce maturationand vessel quiescence. Perictyes are associated with small vesselsand capillaries where they share the basement membrane with theendothelium to provide vascular support. Pericytes are a criticalcomponent of the blood-brain barrier and regulate endothelial cellproliferation, vessel diameter, and vascular permeability.Endothelial cells express Notch1, whereas pericytes express bothNotch1 and Notch3. Here we show that Notch signaling is essentialfor pericyte function. Through genetic manipulation andpharmacological tools we show that Notch regulates pericyterecruitment and pericyte/endothelial cell interactions.Notch1^+/-;Notch3^-/- mutant mice display decreased pericytecoverage and altered pericyte association with the retinal vascularplexus. Notch deficiency is associated with vascular anomalieswhere Notch1^+/-;Notch3-/- mice display retinal arteriovenousmalformations (AVM) characterized by dilated vessels, vasculartangles and arteriovenous shunts that are similar to human brainAVMs. Disruption of pericyte/endothelial cell association isaccompanied by an increase in vascular density, venule enlargement,and increased vascular permeability observed prior to AVMformation. In the ovary, we show that Jagged is essential forpericyte association with the endothelium where inhibition ofJagged-specific Notch activation results in luteal vessel dilationand hemorrhaging following ovarian hyperstimulation. By in vitroanalysis of cultured pericytes we show that Notch1 and Notch3induce plated derived growth factor receptor-β (PDGFR-β) expressionto regulate cell migration. These findings expand the role forNotch in angiogenesis by demonstrating that Notch signaling inpericytes is essential for vascular development andfunction." @default.
- W1489220260 created "2016-06-24" @default.
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- W1489220260 date "2013-01-01" @default.
- W1489220260 modified "2023-09-23" @default.
- W1489220260 title "Notch deficiency leads to arteriovenous malformations and altered pericyte function" @default.
- W1489220260 doi "https://doi.org/10.7916/d8cn7b4k" @default.
- W1489220260 hasPublicationYear "2013" @default.
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