Notch1 and 4 signaling responds to an increasing vascular wall shear stress in a rat model of arteriovenous malformations

Jian Tu*, Yang Li, Zhiqiang Hu

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)

    Abstract

    Notch signaling is suggested to promote the development and maintenance of cerebral arteriovenous malformations (AVMs), and an increasing wall shear stress (WSS) contributes to AVM rupture. Little is known about whether WSS impacts Notch signaling, which is important for understanding the angiogenesis of AVMs. WSS was measured in arteriovenous fistulas (AVF) surgically created in 96 rats at different time points over a period of 84 days. The expression of Notch receptors 1 and 4 and their ligands, Delta1 and 4, Jagged1, and Notch downstream gene target Hes1 was quantified in "nidus" vessels. The interaction events between Notch receptors and their ligands were quantified using proximity ligation assay. There was a positive correlation between WSS and time (r=0.97; P<0.001). The expression of Notch receptors and their ligands was upregulated following AVF formation. There was a positive correlation between time and the number of interactions between Notch receptors and their ligands aftre AVF formation (r=0.62, P<0.05) and a positive correlation between WSS and the number of interactions between Notch receptors and their ligands (r=0.87, P<0.005). In conclusion, an increasing WSS may contribute to the angiogenesis of AVMs by activation of Notch signaling.

    Original languageEnglish
    Article number368082
    Pages (from-to)1-13
    Number of pages13
    JournalBioMed Research International
    Volume2014
    DOIs
    Publication statusPublished - 2014

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