Biology of cerebral arteriovenous malformations with a focus on inflammation

Cerebral arteriovenous malformations (AVMs) entail a significant risk ofintracerebral hemorrhage owing to the direct shunting of arterial blood into thevenous vasculature without the dissipation of the arterial blood pressure. Themechanisms involved in the growth, progression and rupture of AVMs are notclearly understood, but a number of studies point to inflammation as a majorcontributor to their pathogenesis. The upregulation of proinflammatory cytokinesinduces the overexpression of cell adhesion molecules in AVM endothelial cells,resulting in enhanced recruitment of leukocytes. The increased leukocyte-derivedrelease of metalloproteinase-9 is known to damage AVM walls and lead to rupture.Inflammation is also involved in altering the AVM angioarchitecture via theupregulation of angiogenic factors that affect endothelial cell proliferation,migration and apoptosis. The effects of inflammation on AVM pathogenesis arepotentiated by certain single-nucleotide polymorphisms in the genes ofproinflammatory cytokines, increasing their protein levels in the AVM tissue.Furthermore, studies on metalloproteinase-9 inhibitors and on the involvement ofNotch signaling in AVMs provide promising data for a potential basis forpharmacological treatment of AVMs. Potential therapeutic targets and areasrequiring further investigation are highlighted.