Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve
Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve
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DOI：
10.1136/hrt.2003.029785
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发表时间：
2005-06-01
期刊：
影响因子：
5.7
通讯作者：
Spelsberg, TC
中科院分区：
文献类型：
--
作者：
Rajamannan, NM;Subramaniam, M;Spelsberg, TC
目的：研究内皮型一氧化氮合酶（eNOS）的表达与主动脉瓣钙化的关系，以及阿托伐他汀对eNOS表达、亚硝酸盐浓度和主动脉瓣钙化的影响。16只喂食0.5%（wt/wt）高胆固醇饲料; 16只喂食0.5%（wt/wt）胆固醇饲料加阿托伐他汀（2.5 mg/kg/天）。用eNOS免疫组化染色和Western blotting检测主动脉瓣。胆固醇和高敏C反应蛋白（hsCRP）浓度通过标准测定法测定。血清亚硝酸盐浓度测定一氧化氮分析仪。eNOS的定位通过电子显微镜和免疫金标记。结果：与对照组相比，高胆固醇组动物的胆固醇、hsCRP和主动脉瓣钙化均显著增加。通过micro-CT评估，阿托伐他汀可抑制主动脉瓣钙化。eNOS蛋白浓度在对照组和胆固醇组中没有变化，但在阿托伐他汀治疗组中增加。血清亚硝酸盐浓度降低，在高胆固醇血症的动物和阿托伐他汀治疗组增加。结论：这些数据提供的证据表明，慢性实验性高胆固醇血症产生骨矿化的主动脉瓣，这是抑制阿托伐他汀。
Objective: To study in a rabbit model the expression of endothelial nitric oxide synthase ( eNOS) in association with the development of calcification of the aortic valve, and to assess the effects of atorvastatin on eNOS expression, nitrite concentration, and aortic valve calcification.Methods: Rabbits ( n = 48) were treated for three months: 16, forming a control group, were fed a normal diet; 16 were fed a 0.5% (wt/wt) high cholesterol diet; and 16 were fed a 0.5% (wt/wt) cholesterol diet plus atorvastatin (2.5 mg/kg/day). The aortic valves were examined with eNOS immunostains and western blotting. Cholesterol and high sensitivity C reactive protein (hsCRP) concentrations were determined by standard assays. Serum nitrite concentrations were measured with a nitric oxide analyser. eNOS was localised by electron microscopy and immunogold labelling. Calcification in the aortic valve was evaluated by micro-computed tomography (CT).Results: Cholesterol, hsCRP, and aortic valve calcification were increased in the cholesterol fed compared with control animals. Atorvastatin inhibited calcification in the aortic valve as assessed by micro-CT. eNOS protein concentrations were unchanged in the control and cholesterol groups but increased in the atorvastatin treated group. Serum nitrite concentrations were decreased in the hypercholesterolaemic animals and increased in the group treated with atorvastatin.Conclusion: These data provide evidence that chronic experimental hypercholesterolaemia produces bone mineralisation in the aortic valve, which is inhibited by atorvastatin.