Biology of cerebral arteriovenous malformations with a focus on inflammation.

Journal Article (Journal Article;Review)

Cerebral arteriovenous malformations (AVMs) entail a significant risk of intracerebral hemorrhage owing to the direct shunting of arterial blood into the venous vasculature without the dissipation of the arterial blood pressure. The mechanisms involved in the growth, progression and rupture of AVMs are not clearly understood, but a number of studies point to inflammation as a major contributor to their pathogenesis. The upregulation of proinflammatory cytokines induces the overexpression of cell adhesion molecules in AVM endothelial cells, resulting in enhanced recruitment of leukocytes. The increased leukocyte-derived release of metalloproteinase-9 is known to damage AVM walls and lead to rupture. Inflammation is also involved in altering the AVM angioarchitecture via the upregulation of angiogenic factors that affect endothelial cell proliferation, migration and apoptosis. The effects of inflammation on AVM pathogenesis are potentiated by certain single-nucleotide polymorphisms in the genes of proinflammatory cytokines, increasing their protein levels in the AVM tissue. Furthermore, studies on metalloproteinase-9 inhibitors and on the involvement of Notch signaling in AVMs provide promising data for a potential basis for pharmacological treatment of AVMs. Potential therapeutic targets and areas requiring further investigation are highlighted.

Full Text

Duke Authors

Cited Authors

  • Mouchtouris, N; Jabbour, PM; Starke, RM; Hasan, DM; Zanaty, M; Theofanis, T; Ding, D; Tjoumakaris, SI; Dumont, AS; Ghobrial, GM; Kung, D; Rosenwasser, RH; Chalouhi, N

Published Date

  • February 2015

Published In

Volume / Issue

  • 35 / 2

Start / End Page

  • 167 - 175

PubMed ID

  • 25407267

Pubmed Central ID

  • PMC4426734

Electronic International Standard Serial Number (EISSN)

  • 1559-7016

Digital Object Identifier (DOI)

  • 10.1038/jcbfm.2014.179

Language

  • eng

Conference Location

  • United States