Simvastatin promotes atherosclerotic plaque stability in ApoE-deficient mice independently of lipid lowering
Simvastatin promotes atherosclerotic plaque stability in ApoE-deficient mice independently of lipid lowering
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DOI：
10.1161/01.atv.0000036081.01231.16
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发表时间：
2002-11-01
影响因子：
8.7
通讯作者：
Rosenfeld, ME
中科院分区：
文献类型：
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作者：
Bea, F;Blessing, E;Rosenfeld, ME
本研究试图确定辛伐他汀，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，是否对易损动脉粥样硬化斑块具有稳定作用，这些斑块不依赖于它们的降脂能力。方法和结果辛伐他汀（50 mg/kg/天）被给予30周龄的载脂蛋白E缺陷小鼠，这些小鼠表现出无名/头臂动脉内的晚期不稳定动脉粥样硬化病变。将辛伐他汀在饲料中给予不同组的小鼠，持续6、12、18或24周。辛伐他汀治疗12周、18周和24周后显著升高血清胆固醇。治疗12周和24周后，无名动脉中动脉粥样硬化病变的平均横截面积增加，同时血清胆固醇增加。然而，组织学分析切片的无名动脉染色Movat和冯科萨染色表明，减少了49%的频率斑块内出血和减少了56%的频率钙化，这两个标志先进的和不稳定的动脉粥样硬化plakes. Conclusions这些数据表明，尽管增加血清胆固醇和病变大小，辛伐他汀对晚期动脉粥样硬化病变具有稳定作用。
Objective-This study sought to determine whether simvastatin, a 3-hydroxy-3-methylgtutaryl coenzyme A reductase inhibitor, has stabilizing effects on vulnerable atherosclerotic plaques that Lire independent of their lipid-lowering capabilities.Methods and Results-Simvastatin (50 mg/kg per day) was administered to 30-week-old apolipoprotein E-deficient mice exhibiting advanced unstable atherosclerotic lesions within the innominate/brachiocephalic artery. Simvastatin was administered in the chow to separate groups of mice for 6, 12, 18, or 24 weeks. Simvastatin significantly increased serum cholesterol after 12, 18, and 24 weeks of treatment. The average cross-sectional area of atherosclerotic lesion increased in the innominate artery after 12 and 24 weeks of treatment, concomitant with the increase in serum cholesterol. However, histological analysis of sections of the innominate artery stained with Movat and von Kossa stains demonstrated a 49% reduction in the frequency of intraplaque hemorrhage and a 56% reduction in the frequency of calcification, both markers of advanced and unstable atherosclerotic plaques.Conclusions-These data suggest that despite an increase in serum cholesterol and lesion size, simvastatin has stabilizing effects on advanced atherosclerotic lesions.