Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations.

Journal Article (Journal Article;Review)

Brain arteriovenous malformations (AVMs) cause intracranial hemorrhage (ICH), especially in young adults. Molecular characterization of lesional tissue provides evidence for involvement of both angiogenic and inflammatory pathways, but the pathogenesis remains obscure and medical therapy is lacking. Abnormal expression patterns have been observed for proteins related to angiogenesis (e.g., vascular endothelial growth factor, angiopoietin-2, matrix metalloproteinase-9), and inflammation (e.g., interleukin-6 [IL-6] and myeloperoxidase). Macrophage and neutrophil invasion have also been observed in the absence of prior ICH. Candidate gene association studies have identified a number of germline variants associated with clinical ICH course and AVM susceptibility. A single nucleotide polymorphism (SNP) in activin receptor-like kinase-1 (ALK-1) is associated with AVM susceptibility, and SNPs in IL-6, tumor necrosis factor-alpha (TNF-alpha), and apolipoprotein-E (APOE) are associated with AVM rupture. These observations suggest that even without a complete understanding of the determinants of AVM development, the recent discoveries of downstream derangements in vascular function and integrity may offer potential targets for therapy development. Further, biomarkers can now be established for assessing ICH risk. These data will generate hypotheses that can be tested mechanistically in model systems, including surrogate phenotypes, such as vascular dysplasia and/or models recapitulating the clinical syndrome of recurrent spontaneous ICH.

Full Text

Duke Authors

Cited Authors

  • Kim, H; Marchuk, DA; Pawlikowska, L; Chen, Y; Su, H; Yang, GY; Young, WL

Published Date

  • 2008

Published In

Volume / Issue

  • 105 /

Start / End Page

  • 199 - 206

PubMed ID

  • 19066109

Pubmed Central ID

  • PMC2640934

International Standard Serial Number (ISSN)

  • 0065-1419

Digital Object Identifier (DOI)

  • 10.1007/978-3-211-09469-3_38


  • eng

Conference Location

  • Austria