The role of the renin--angiotensin system in the pathogenesis of intracranial aneurysms.

Introduction: Recent work has begun to elucidate the pathogenesis of intracranial aneurysms (IA) and has shown that many genes are involved in the risk for this condition. There has also been increasing research interest in the renin-angiotensin system (RAS) in the brain and it involvement in a range of cardiovascular and neurological disorders. The possibility that the RAS is implicated in the pathogenesis of IA merits further investigation. The aim of this article is to review the literature on the pathogenesis of IA and the pathophysiological significance of the brain RAS, and to identify directions for research into their association.

Methods And Results: A survey of the literature in these fields shows that although factors contributing to systemic hypertension predispose to IA, a large number of genes involved in endothelial cell adhesion, smooth muscle activity, extracellular matrix dynamics and the inflammatory and immune responses are also implicated. The brain RAS has a significant role in regulating blood pressure and in maintaining cerebrovascular autoregulation, but angiotensin II receptors are also involved in the maintenance of endothelial cell and vascular smooth muscle function and in the inflammatory response in the brain.

Conclusions: There is strong, albeit largely circumstantial, evidence in the literature for a relationship between the brain RAS and the formation of IA. Research on the association between polymorphisms in RAS-related genes and the incidence of unruptured and ruptured IA is indicated.