Abstract
Cerebral aneurysm (CA) can cause subarachnoid hemorrhage which is a devastating illness with a high mortality and morbidity. Given its high prevalence and susceptibility to subarachnoid hemorrhage, treatment of CA is socially important. However, there is currently no medical treatment of CA because detailed mechanisms of CA formation remain unclear. We recently found that NF-kappa B (NF-κB) was a mediator of inflammation in CA walls. NF-κB was activated during CA formation mainly in the endothelial cells and macrophages which were main inflammatory cells in CA walls. Activated NF-κB regulated the MCP-1 expression resulting in the accumulation of macrophage in CA walls. Next, we inhibited NF-κB activity by two different strategies, p50 deficient mice and decoy oligodeoxyneucleotides. Both inhibitions resulted in the effective suppression of CA formation through the decreased inflammation suggesting that NF-κB played the crucial role on CA formation as a mediator of inflammation. Statin (HMG-CoA reductase inhibitor) is widely used as a powerful cholesterol lowering drug. Statin also has an anti-NF-κB activity known as the pleiotrophic effect. Statin orally given to rat CA model effectively inhibited the CA growth and thinning of media. These results suggest that statin is a leading candidate of drugs to treat human CA.
