title: Molecular basis for intracranial aneurysm formation.
abstract: Intracranial aneurysm (IA) is a socially important disease both because it has a high prevalence and because of the severity of resultant subarachnoid hemorrhages after IA rupture. The major concern of current IA treatment is the lack medical therapies that are less invasive than surgical procedures for many patients. The current situation is mostly caused by a lack of knowledge regarding the regulating mechanisms of IA formation. Hemodynamic stress, especially high wall shear stress, loaded on arterial bifurcation sites is recognized as a trigger of IA formation from studies performed in the field of fluid dynamics. On the other hand, many studies using human specimens have also revealed the presence of active inflammatory responses, such as the infiltration of macrophages, in the pathogenesis of IA. Because of these findings, recent experimental studies, mainly using animal models of IA, have revealed some of the molecular mechanisms linking hemodynamic stress and long-lasting inflammation in IA walls. Currently, we propose that IA is a chronic inflammatory disease regulated by a positive feedback loop consisting of the cyclooxygenase (COX)-2 - prostaglandin (PG) E2 - prostaglandin E receptor 2 (EP2) - nuclear factor (NF)-κB signaling pathway triggered under hemodynamic stress and macrophage infiltration via NF-κB-mediated monocyte chemoattractant protein (MCP)-1 induction. These findings indicate future directions for the development of therapeutic drugs for IAs.
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Fukuda
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Aoki
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D055808:Drug Discovery; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D002532:Intracranial Aneurysm / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D013314:Stress, Mechanical