BACKGROUND AND PURPOSE: Mechanisms of initiation, progression and rupture of cerebral aneurysms have not yet been fully understood despite its clinical significance. Matrix metalloproteinases (MMPs) are a family of proteinases which are involved in the remodeling of vascular walls. In the present study, we investigated the significance of MMPs in the progression of cerebral aneurysms. METHODS: Cerebral aneurysms were experimentally induced in 7-week-old male Sprague-Dawley rats. MMP-2 and MMP-9 expression was examined by immunohistochemistry and RT-PCR. Gelatinase activity in aneurysmal walls was assessed by in situ zymography. A selective inhibitor for MMP-2, -9 and -12, tolylsam, was used to examine the effect of inhibition of MMP-2 and MMP-9. RESULTS: Macrophages infiltrated in arterial walls of experimentally induced rat cerebral aneurysms and expressed MMP-2 and -9. Macrophage infiltration and MMP expression was increased with the progression of aneurysms. Gelatinase activity attributable to MMP-2 and MMP-9 increased in arterial walls of rat cerebral aneurysms. Furthermore, tolylsam reduced the ratio of advanced aneurysms in our rat model. CONCLUSIONS: These data suggest that macrophage-derived MMP-2 and -9 may play an important role in the progression of cerebral aneurysms. The findings of this study will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease.
BACKGROUND AND PURPOSE: Mechanisms of initiation, progression and rupture of cerebral aneurysms have not yet been fully understood despite its clinical significance. Matrix metalloproteinases (MMPs) are a family of proteinases which are involved in the remodeling of vascular walls. In the present study, we investigated the significance of MMPs in the progression of cerebral aneurysms. METHODS:Cerebral aneurysms were experimentally induced in 7-week-old male Sprague-Dawley rats. MMP-2 and MMP-9 expression was examined by immunohistochemistry and RT-PCR. Gelatinase activity in aneurysmal walls was assessed by in situ zymography. A selective inhibitor for MMP-2, -9 and -12, tolylsam, was used to examine the effect of inhibition of MMP-2 and MMP-9. RESULTS: Macrophages infiltrated in arterial walls of experimentally induced ratcerebral aneurysms and expressed MMP-2 and -9. Macrophage infiltration and MMP expression was increased with the progression of aneurysms. Gelatinase activity attributable to MMP-2 and MMP-9 increased in arterial walls of ratcerebral aneurysms. Furthermore, tolylsam reduced the ratio of advanced aneurysms in our rat model. CONCLUSIONS: These data suggest that macrophage-derived MMP-2 and -9 may play an important role in the progression of cerebral aneurysms. The findings of this study will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease.
Authors: T Aoki; M Nishimura; T Matsuoka; K Yamamoto; T Furuyashiki; H Kataoka; S Kitaoka; R Ishibashi; A Ishibazawa; S Miyamoto; R Morishita; J Ando; N Hashimoto; K Nozaki; S Narumiya Journal: Br J Pharmacol Date: 2011-07 Impact factor: 8.739
Authors: Kimon Bekelis; Joanna S Kerley-Hamilton; Amy Teegarden; Craig R Tomlinson; Rachael Kuintzle; Nathan Simmons; Robert J Singer; David W Roberts; Manolis Kellis; David A Hendrix Journal: J Neurosurg Date: 2016-02-26 Impact factor: 5.115
Authors: Robert M Starke; Nohra Chalouhi; Dale Ding; Daniel M S Raper; M Sean Mckisic; Gary K Owens; David M Hasan; Ricky Medel; Aaron S Dumont Journal: Transl Stroke Res Date: 2013-10-10 Impact factor: 6.829