부산대학교 도서관

Aims: The loss of elastin and subsequent weakening of the aneurysmal aortic wall is mediated by high levels of matrix metalloproteases and inflammatory cytokines. HMG CoA reductase inhibitors ('statins') may offer a pharmacotherapeutic strategy to prevent aneurysm expansion due to inhibition of both MMP formation and cytokine secretion. Methods: Elastin degradation was examined in a porcine model of aneurysmal disease. Sections of 1 cm[sup 2] of healthy porcine aorta were treated with elastase for 24 h to initiate an inflammatory and proteolytic response. Following organ culture with incremental doses of simvastatin for 14 days, tissue was harvested for histological examination and MMP activity. The inflammatory response within aortic tissue was examined using full thickness human aneurysmal explants cultured in simvastatin for 48 h. Cytokine production was measured in the conditioned medium by ELISA, and MMP activity quantified by substrate gel zymography. Results: Addition of simvastatin to the culture medium resulted in preservation of elastin and reduction in the levels of MMPs and interleukin-6. Conclusions: Simvastatin has beneficial effects on the inflammatory and proteolytic processes within the aneurysmal aortic wall, and has the potential to retard aneurysm expansion in clinical trials. [ABSTRACT FROM AUTHOR]