Molecular mechanisms of cerebral aneurysmal formation

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The pathogenesis of cerebral aneurysm has not been-fully understood. We have developed experimental cerebral aneurysmal models in rats and mice and analyzed expressed proteins and messenger RNAs during the process of cerebral aneurismal formation. We confirmed the decrease in eNOS in the endothelium and increase in iNOS in the smooth muscle during the process, and demonstrated that an inhibitor of iNOS and the disruption of iNOS gene inhibited the aneurysmal formation. We also demonstrated increased active MMP-2 and 9 during the process and the knockout of MMP-9 decreased the formation of cerebral aneurysm. We also detected by PCR the expression of specific molecules which are related to vascular remodeling. Finally we analyzed the candidate genes which had high linkage to aneurysmal formation in highly-aggregated Japanese families.