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BioMed Research International
Volume 2014, Article ID 368082, 13 pages
http://dx.doi.org/10.1155/2014/368082
Research Article

Notch1 and 4 Signaling Responds to an Increasing Vascular Wall Shear Stress in a Rat Model of Arteriovenous Malformations

1Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia
2Department of Neurosurgery, The 9th Medical Clinical College of Beijing University, Beijing 100038, China

Received 27 September 2013; Accepted 11 December 2013; Published 20 January 2014

Academic Editor: Robert M. Starke

Copyright © 2014 Jian Tu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 (; ). 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 (, ) and a positive correlation between WSS and the number of interactions between Notch receptors and their ligands (, ). In conclusion, an increasing WSS may contribute to the angiogenesis of AVMs by activation of Notch signaling.