Biology of cerebral arteriovenous malformations with a focus on inflammation

Nikolaos Mouchtouris, Pascal M. Jabbour, Robert M. Starke, David M. Hasan, Mario Zanaty, Thana Theofanis, Dale Ding, Stavropoula I. Tjoumakaris, Aaron S. Dumont, George M. Ghobrial, David Kung, Robert H. Rosenwasser, Nohra Chalouhi

Research output: Contribution to journalReview articlepeer-review

94 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)167-175
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number2
DOIs
StatePublished - Feb 2 2015
Externally publishedYes

Keywords

  • angiogenesis
  • arteriovenous malformations
  • AVM
  • endothelial cell
  • inflammation
  • intracerebral hemorrhage

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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