2026-04-29T04:09:43Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/172072024-09-21T11:46:27Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Nadeem, Taliha
author
Bogue, Wil
author
Bigit, Bianca
author
Cuervo, Henar
2024-01-17T12:53:28Z
2024-01-17T12:53:28Z
2020-11-05
JCI Insight. 2020 Nov 5;5(21):e125940.
http://hdl.handle.net/20.500.12105/17207
33148887
10.1172/jci.insight.125940
2379-3708
JCI insight
Arteriovenous malformations (AVMs) are high-flow lesions directly connecting arteries and veins. In the brain, AVM rupture can cause seizures, stroke, and death. Patients with AVMs exhibit reduced coverage of the vessels by pericytes, the mural cells of microvascular capillaries; however, the mechanism underlying this pericyte reduction and its association with AVM pathogenesis remains unknown. Notch signaling has been proposed to regulate critical pericyte functions. We hypothesized that Notch signaling in pericytes is crucial to maintain pericyte homeostasis and prevent AVM formation. We inhibited Notch signaling specifically in perivascular cells and analyzed the vasculature of these mice. The retinal vessels of mice with deficient perivascular Notch signaling developed severe AVMs, together with a significant reduction in pericytes and vascular smooth muscle cells (vSMC) in the arteries, while vSMCs were increased in the veins. Vascular malformations and pericyte loss were also observed in the forebrain of embryonic mice deficient for perivascular Notch signaling. Moreover, the loss of Notch signaling in pericytes downregulated Pdgfrb levels and increased pericyte apoptosis, pointing to a critical role for Notch in pericyte survival. Overall, our findings reveal a mechanism of AVM formation and highlight the Notch signaling pathway as an essential mediator in this process.
eng
Deficiency of Notch signaling in pericytes results in arteriovenous malformations.
journal article
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URL
https://repisalud.isciii.es/bitstreams/9b59bde0-ffb6-477d-96a4-f49fcf11fe90/download
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application/pdf
Deficiency of Notch signaling_JCI Insight_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/28711746-88fd-4962-b33d-281e05e7939f/download
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e74d4ed78ce91d73a9dcfeb11da55cc2
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Deficiency of Notch signaling_JCI Insight_2020.pdf.txt