title: Notch1 and 4 signaling responds to an increasing vascular wall shear stress in a rat model of arteriovenous malformations.
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.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia.
authors.forename: Jian
authors.identifier: 0000-0002-8478-5292
authors.initials: J
authors.lastname: Tu
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The 9th Medical Clinical College of Beijing University, Beijing 100038, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001164:Arteriovenous Fistula / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001165:Arteriovenous Malformations / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006439:Hemodynamics; D018398:Homeodomain Proteins / Q000378:metabolism; D008024:Ligands; D008297:Male; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000378:metabolism*; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000378:metabolism*; D012039:Regional Blood Flow; D033081:Shear Strength; D015398:Signal Transduction; D013314:Stress, Mechanical; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053148:Caspase 3; D018398:Homeodomain Proteins; D008024:Ligands; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051881:Receptor, Notch1; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C497763:Notch1 protein, rat; C560417:Notch4 protein, rat