Fluvastatin alters platelet aggregability in patients with hypercholesterolemia - Possible improvement of intraplatelet redox imbalance via HMG-CoA reductase
Fluvastatin alters platelet aggregability in patients with hypercholesterolemia - Possible improvement of intraplatelet redox imbalance via HMG-CoA reductase
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DOI：
10.1161/atvbaha.106.128793
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发表时间：
2007-06-01
影响因子：
8.7
通讯作者：
Imaizumi, Tsutomu
中科院分区：
文献类型：
--
作者：
Haramaki, Nobuya;Ikeda, Hisao;Imaizumi, Tsutomu
背景-高胆固醇血症增强血小板聚集性。他汀类药物对心血管事件有有益作用。本研究的目的是调查他汀类药物是否抑制血小板聚集，如果是这样，mechanism.Methods和Results-Twelve高胆固醇血症患者前瞻性随机交叉设计接受氟伐他汀（20 mg/d）或考来替胺（3000 mg/d）12周。受试者转换至另一组，再治疗12周。在第一次和第二次处理之前和之后，进行实验。11名年龄匹配的血脂正常的志愿者作为对照。测定ADP诱导的血小板聚集、血小板源性一氧化氮（PDNO）释放、血小板内GSH和GSSG水平以及血小板聚集过程中血小板内硝基酪氨酸的产生。氟伐他汀和考来替胺同样降低高胆固醇血症患者的总胆固醇和低密度脂蛋白胆固醇水平。治疗前，高胆固醇血症患者的血小板聚集率高于胆固醇正常者，氟伐他汀可改变血小板聚集率。PDNO释放，血小板内谷胱甘肽水平，GSH/GSSG比在高胆固醇血症低于正常胆固醇血症治疗前，氟伐他汀增加。血小板内硝基酪氨酸的形成在高胆固醇血症比在正常胆固醇血症，并减少氟伐他汀。考来替胺没有这种作用。体外应用氟伐他汀呈剂量依赖性抑制血小板聚集。此外，在体外应用氟伐他汀剂量依赖性地抑制血小板硝基酪氨酸的表达和氟伐他汀的抑制作用被逆转与geranylgeranylpyrophosphato. Conclusions预孵育氟伐他汀改变血小板聚集性高胆固醇血症患者在一个胆固醇降低独立的方式，这是部分介导的改善血小板内氧化还原失衡。
Background-Hypercholesterolemia enhances platelet aggregability. Statins have beneficial effects on cardiovascular events. The purpose of this study is to investigate whether statins inhibit platelet aggregation and, if so, the mechanisms.Methods and Results-Twelve patients with hypercholesterolemia were prospectively randomized in a crossover design to receive either fluvastatin (20 mg/d) or colestimide (3000 mg/d) for 12 weeks. The subjects were switched to the opposite arm for additional 12 weeks. Before and after first and second treatments, experiments were performed. Eleven age-matched volunteers with normal lipid profiles served as controls. ADP-induced platelet aggregation, platelet-derive nitric oxide (PDNO) release, intraplatelet levels of GSH and GSSG, and intraplatelet nitrotyrosine production during platelet aggregation were measured. Fluvastatin and colestimide equally lowered total and low density lipoprotein cholesterol levels in hypercholesterolemia. Platelet aggregation was greater in hypercholesterolemia than in normocholesterolemia before treatment and was altered by fluvastatin. PDNO release, intraplatelet glutathione level, and GSH/GSSG ratio were lower in hypercholesterolemia than in normocholesterolemia before treatment and were increased by fluvastatin. Intraplatelet nitrotyrosine formation was greater in hypercholesterolemia than in normocholesterolemia, and decreased by fluvastatin. Colestimide did not have such effects. In vitro application of fluvastatin dose-dependently inhibited platelet aggregation. Furthermore, in vitro application of fluvastatin dose-dependently inhibited platelet nitrotyrosine expressions and the inhibitory effects by fluvastatin were reversed by preincubation with geranylgeranylpyrophosphate.Conclusions-Fluvastatin altered platelet aggregability in hypercholesterolemic patients in a cholesterol-lowering independent manner, which was partly mediated by the improvement of intraplatelet redox imbalance.