Dec 5, 2019

RNA-Sequencing Highlights Inflammation and Impaired Integrity of the Vascular Wall in Brain Arteriovenous Malformations

Stroke; a Journal of Cerebral Circulation
Allard J HauerCatharina J M Klijn

Abstract

Background and Purpose- Interventional treatment of unruptured brain arteriovenous malformations (BAVMs) has become increasingly controversial. Because medical therapy is still lacking, we aimed to obtain insight into the disease mechanisms implicated in BAVMs and to identify potential targets for medical treatment to prevent rupture of a BAVM. Methods- We used next-generation RNA sequencing to identify differential expression on a transcriptome-wide level comparing tissue samples of 12 BAVMs to 16 intracranial control arteries. We identified differentially expressed genes by negative binominal generalized log-linear regression (false discovery rate corrected P<0.05). We selected 10 genes for validation using droplet digital polymerase chain reaction. We performed functional pathway analysis accounting for potential gene-length bias, to establish enhancement of biological pathways involved in BAVMs. We further assessed which Gene Ontology terms were enriched. Results- We found 736 upregulated genes in BAVMs including genes implicated in the cytoskeletal machinery and cell-migration and genes encoding for inflammatory cytokines and secretory products of neutrophils and macrophages. Furthermore, we found 498 genes downregulated i...Continue Reading

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Citations

Mentioned in this Paper

Rupture
Genome-Wide Association Study
Study
Biochemical Pathway
Transforming Growth Factor beta
Protein Digestion
Genes
Sequence Determinations, RNA
Brain
Extracellular Matrix

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