脳動脈瘤の成因:実験的脳動脈瘤誘発動物モデルを用いたその発生機序の解明: NOを中心に
概要
Cerebral saccular aneurysm is a major cause of subarachnoid hemorrhage, one of the cerebrovascular diseases with the highest mortality. The mechanisms underlying the development of aneurysm, however, still remain unclear. We have made a series of reports on an animal model of experimentally induced cerebral aneurysms, which resemble human cerebral aneurysms in their location and morphology. The objective of this brief review is to introduce our evidence about the pathogenesis of cerebral aneurysms using the experimentally induced cerebral aneurysm model, particularly focused upon the role of NO and shear stress on degenerative changes of the arterial wall during the aneurysm development.<BR>In our model, cerebral aneurysms are induced in rats, monkeys, and mice by ligation of unilateral common carotid artery and renal hypertension, suggesting that an increase in hemodynamic stress is a key requirement for the aneurysm development. Our morphological and molecular studies suggest that increased wall shear stress, iNOS-derived NO, MMP-2 & 9, cathepsin B, NF-κ B, interleukin-1 β, and endothelin B receptor are associated with the progression of cerebral aneurysms. Statin and Nifedipine may be possible drugs for the prevention of cerebral aneurysm development.