The effect of atorvastatin on erythrocyte membranes and serum lipids in patients with type-2 hypercholesterolemia
The effect of atorvastatin on erythrocyte membranes and serum lipids in patients with type-2 hypercholesterolemia
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DOI：
10.1007/s00228-002-0507-9
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发表时间：
2002-11-01
影响因子：
2.9
通讯作者：
Franiak, I
中科院分区：
文献类型：
--
作者：
Koter, M;Broncel, M;Franiak, I
背景：他汀类药物对临床事件的有益影响可能涉及改善内皮功能障碍、斑块稳定性、血栓形成和炎症反应的机制。为探讨阿托伐他汀对家族性高胆固醇血症(FH)患者血液流变学的影响，我们对家族性高胆固醇血症(FH)患者的血脂浓度、红细胞胆固醇含量、脂质过氧化和红细胞膜流动性进行了前瞻性研究。本研究旨在探讨阿托伐他汀对FH患者红细胞膜结构及降脂疗效的影响。材料、方法与研究对象：31例FH患者及20例健康体检者。该计划持续了20周。在前8周，患者只接受低血脂饮食，在随后的12周，在饮食的同时，他们每天服用10毫克阿托伐他汀。分别于用药前、用药后4周和12周进行实验室检查。采用自旋标记法测定红细胞膜流动性。结果：阿托伐他汀治疗后，血清总胆固醇浓度从基础状态下的310+/-29 mg/dl降至治疗结束时的203+/-34 mg/dl(P<；0.00 1)，低密度脂蛋白胆固醇浓度从225+/-30 mg/dl降至126+/-30 mg/dl(P<；0.00 1)。观察到的血脂变化与红细胞膜胆固醇的显著下降有关，治疗12周后，红细胞膜胆固醇从2.24+/-1.69降至1.17+/-0.75 mg/mg蛋白质(P<；0.00 1)。治疗4周后红细胞膜脂质过氧化水平由基础值0.171+/-0.097降至0.100+/-0.024 mmoP/mg蛋白(P<；0.05)，12周后降至0.057+/-0.020 mmoL/mg蛋白(p<；0.001)；0.02)和2.43+/-0.87mmolg Hb(P<；0.001)。用S参数估算了膜在第五碳原子深度的流动性。高胆固醇血症红细胞中的阿托伐他汀可将表层流动性从0.758+/-0.009提高到对照组的0.744+/-0.009(P<；0.001)。结论：阿托伐他汀治疗可逆转红细胞膜性质的改变。可改善FH患者的血液流变学。这种血液性质的改善可能有助于阿托伐他汀对严重高脂血症和动脉粥样硬化性血管疾病患者心血管风险的众所周知的有益效果。
Background: The beneficial effects of statins on clinical events may involve mechanisms that modify endothelial dysfunction, plaque stability, thrombus formation, and inflammatory responses. To determine the effect of atorvastatin on blood rheology in patients with familial hypercholesterolemia (FH), we prospectively studied serum lipid concentration, red cell cholesterol content, lipid peroxidation and erythrocyte membrane fluidity. The aim of this paper was to evaluate the effects of atorvastatin therapy on the erythrocyte membrane structure and the hypolipemic efficacy in patients with FH.Materials, methods and subjects studied: The study involved 31 patients with FH and 20 healthy individuals as a control group. The program lasted 20 weeks. For the first 8 weeks, the patients were on a hypolipemic diet only and for the subsequent 12 weeks, alongside the diet they were given 10 mg atorvastatin per day. Laboratory tests were carried out before and after 4 weeks and 12 weeks of the pharmacological treatment. Erythrocyte membrane fluidity was determined using the spin labeled method. The peroxidation of lipids was measured in whole erythrocytes as well as in erythrocyte plasma membranes by means of the thiobarbituric acid technique.Results: Treatment with atorvastatin reduced serum total cholesterol concentration from 310 +/- 29 mg/dl in a basal situation to 203 +/- 34 mg/dl (P < 0.00 1) at the end of the treatment and low-density lipoprotein (LDL) cholesterol concentration from 225 +/- 30 mg/dl to 126 +/- 30 mg/dl (P < 0.00 1), respectively. The changes observed in the plasma lipids correlate with a significant decrease in erythrocyte membrane cholesterol, from 2.24 +/- 1.69 to 1.17 +/- 0.75 mg/mg protein (P < 0.00 1) after 12 weeks of treatment. The lipid peroxidation in membranes of erythrocytes was lowered from the basal value 0.171 +/- 0.097 to 0.100 +/- 0.024 mmol/mg protein (P < 0.05) after 4 weeks of treatment and to 0.057 +/- 0.020 mmol/mg protein (P < 0.001) after 12 weeks of treatment, and in total erythrocytes from 4.78 +/- 1.49 to 3.99 +/- 1.39 mmol/g Hb (P < 0.02) and 2.43 +/- 0.87 mmol/g Hb (P < 0.001), respectively. The membrane fluidity was estimated by means of parameter S at the depth of the fifth carbon atom. Atorvastatin in hypercholesterolemic erythrocytes enhances the fluidity of the superficial layer from 0.758 +/- 0.009 up to the values observed in the control group 0.744 +/- 0.009 (P < 0.001). There is no impact on the microviscosity of the hydrophobic core observed.Conclusion: Our findings suggest that the atorvastatin therapy reverses the alteration of erythrocyte plasma membrane properties. It may improve blood rheology in patients with FH. This improvement in blood properties may contribute to the well-known beneficial effects of atorvastatin on cardiovascular risk in patients with severe hyperlipidemia and atherosclerotic vascular disease.