Dr. Corinne Nielsen
Dr. Corinne Nielsen, Assistant Professor of Biological Sciences, spoke at the national conference of the North American Vascular Biology Organization in Newport, RI, in October.
Her talk was on “Effects on perivascular cells during Notch mediated brain arteriovenous malformation.”
Abstract: Brain arteriovenous malformation (AVM) is a neurovascular disease characterized by arteriovenous (AV) shunting, which connects arteries directly to veins and often leads to hemorrhage, stroke, and neurological deficit. Treatment options to reduce or remove brain AVM vessels are limited and high-risk, and molecular based therapies are lacking. We use a mouse model of brain AVM, in which Rbpj – a transcriptional regulator of canonical Notch signaling – is selectively deleted from postnatal endothelium in mice. Mutant mice develop AV shunts, display abnormal endothelial cell gene expression, and show altered smooth muscle cell coverage. Pericytes, perivascular cells closely associated with blood vessels, are necessary for vascular development and homeostasis and are critical in the brain, where they are involved in regulating blood flow and establishing the blood:brain barrier. A role for pericytes during neurovascular pathogenesis is less clear – while some studies associate decreased pericyte coverage with select neurovascular diseases, others suggest increased pericyte infiltration in response to hypoxia or traumatic brain injury. We present data that show consequences to pericytes in Rbpj-brain AVM: 1) total pericyte area is increased, 2) pericyte expansion keeps pace with pathological endothelial expansion, and 3) pericyte coverage is regionally regulated. These results suggest that pericytes are affected during the pathogenesis of Rbpj mediated brain AVM. By understanding how these cells are involved in and/or influenced by brain AVM, we hope to identify pericytes as potential therapeutic targets for Rbpj/Notch associated brain AVM.
Site of the North American Vascular Biology Organization in Newport, RI. Photo courtesy of NAVRO
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