Anti-inflammatory effect of cerivastatin in vascular injury independent of serum cholesterol and blood pressure lowering effects in mouse model

摘要

Objective: To observe the anti-inflammatory effect of cerivastatin in a mouse model of vascular injury and its cholesterol-lowering effect. Methods: We developed a mouse model of vascular remodeling induced by polyethylene cuff placement and determined the anti-inflammatory effects of cerivastatin in wild mice. Cerivastatin was given by Alzet micro-osmotic minipumps implanted intraperitoneally at the same time as cuff placement at doses of 0.1 mg/kg, 0.5 mg/kg and 1 mg/kg per day, respectively for 2 weeks after cuff placement. The insufficient doses of Cerivastatin to lower serum cholesterol and systolic blood pressure through the neointimal formation and BrdU index were investigated in mouse femoral injury artery induced by cuff-placement. Results: There was a little change in serum cholesterol by the treatment with cerivastatin, the cross-sectional area of intima of injured femoral artery was significantly increased, the neointima formation was significantly increased by the cuff-induced vascular injury at day 14. The neointimal formation and BrdU index were inhibited in the 1 mg/kg cerivastatin, but not in the 0.1 mg/kg and 0.5 mg/kg cerivastatin. Furthermore, 1 mg/kg of cerivastatin significantly inhibited the expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) without lowering serum cholesterol.Conclusions: These results suggest that cerivastatin can inhibit vascular inflammation and the proliferation of vascular smooth muscle cells (VSMCs) through its lipid-lowering independent action. Such effects of cerivastatin may be an important mechanism, by which it prevents the development of atherosclerotic lesions.