Simvastatin inhibits lymphocyte function in normal subjects and patients with cardiovascular disease
Simvastatin inhibits lymphocyte function in normal subjects and patients with cardiovascular disease
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DOI：
10.1016/j.atherosclerosis.2004.03.018
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发表时间：
2004-08-01
期刊：
影响因子：
5.3
通讯作者：
Jardine, AG
中科院分区：
文献类型：
--
作者：
Hillyard, DZ;Cameron, AJM;Jardine, AG
HMG-CoA还原酶抑制剂（他汀类药物）阻断甲羟戊酸途径，阻止胆固醇和类异戊二烯的生物合成。我们研究了辛伐他汀对正常人和心血管疾病患者淋巴细胞的影响，以提供他汀类药物体内作用的模型。13名健康志愿者每天用40 mg辛伐他汀治疗，随后平均总胆固醇降低23%（S.D. +/- 11.7%）和平均LDL-胆固醇降低36%（S.D. +/- 16.3%）。淋巴细胞脂筏水平，代表林恩和Fyn，也降低辛伐他汀。辛伐他汀治疗没有改变离体T淋巴细胞增殖。然而，在体外加入1 μ M辛伐他汀使T淋巴细胞增殖减少39%（S.D. +/-18.1%）和异戊烯基转移酶抑制剂的组合使增殖降低19%（S.D. +/- 22.7%）。我们还评估了自然杀伤（NK）细胞（T淋巴细胞亚群）的细胞毒性。离体NK细胞细胞毒性降低30%（S.D. +/- 33.6%）和56%（S.D. +/-24.68%）。在接受他汀类药物治疗的心血管疾病患者中，观察到T细胞增殖和NK细胞毒性的体外显著降低。NK细胞参与动脉粥样硬化的发病机制，因此他汀类药物治疗对NK细胞细胞毒性的影响可能有助于他汀类药物在心血管疾病中的益处。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
HMG-CoA reductase inhibitors (statins) block the mevalonate pathway, preventing biosynthesis of cholesterol and isoprenoids. We investigated the effect of simvastatin on lymphocytes from normal human subjects and cardiovascular disease patients in order to provide a model for the in vivo actions of statins. Thirteen healthy volunteers were treated with 40 mg per day of simvastatin following which mean total cholesterol was reduced by 23% (S.D. +/- 11.7%) and mean LDL-cholesterol by 36% (S.D. +/- 16.3%). Lymphocyte lipid raft levels, represented by Lyn and Fyn, were also reduced by simvastatin. Treatment with simvastatin did not alter ex vivo T-lymphocyte proliferation. However, the in vitro addition of 1 muM simvastatin reduced T-lymphocyte proliferation by 39% (S.D. +/- 18.1%) and a combination of prenyl transferase inhibitors reduced proliferation by 19% (S.D. +/- 22.7%). We also assessed the cytotoxicity of natural killer (NK) cells-a T-lymphocyte subset. NK cell cytotoxicity ex vivo was reduced by 30% (S.D. +/- 33.6%) following oral simvastatin treatment and by 56% (S.D. +/- 24.68%) after the in vitro addition of 1 muM simvastatin. Significant ex vivo reductions in T-cell proliferation and NK cell cytotoxicity were observed in patients with cardiovascular disease on treatment with statins. NK cells have been implicated in the pathogenesis of atherosclerosis, so the effect of statin therapy on NK cell cytotoxicity may contribute to the benefits of statins in cardiovascular disease. (C) 2004 Elsevier Ireland Ltd. All rights reserved.