Abstract 16332: A Novel Mouse Model of Hemorrhagic Arteriovenous Malformation in the Brain and Spinal Cord
Hemorrhage from neurological arteriovenous malformation (AVM) may cause severe neurological deficit or death. A limit in studying neurological AVM and its rupture has been the lack of appropriate mouse models. The only neurological AVM model previously available showed no hemorrhage and a very minor phenotype. We recently developed a novel mouse AVM model by crossing activin receptor-like kinase 1 (ALK1, Acvrl1) conditional knockout mice and tissue specific Cre-deleter mice. These novel mice develop AVMs predominantly in neurological tissues and often suffer from paralyzation or death within the first ten weeks of life due to internal hemorrhages. In order to further analyze the pathogenesis of these AVMs, we investigated the genes induced in the AVM lesions. First, we used qPCR to analyze specific candidate genes in AVMs. We found that angiogenic genes including angiopoietin 2 (Agpt2), platelet derived growth factor-B, vascular endothelial growth factor as well as inflammatory genes such as interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α, and cyclooxygenase-2 (Cox-2) are upregulated in the brain tissue of conditional deletion mice. Immunohistochemical staining was performed to locate the protein product of each gene within the AVM lesions. Through the staining we confirmed Agpt2, IL-1β, and Cox-2 were expressed within the AVM walls, predominantly in the endothelial cells. This data suggests that angiogenic and inflammatory genes do indeed play an important role in the AVM pathogenesis and potentially its rupture. In the future, we aim to elucidate the roles these genes play in AVM development/rupture as well as whether pharmacologically attenuating these genes will help prevent AVM development and/or rupture.
- © 2011 by American Heart Association, Inc.