Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment
Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment
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DOI：
10.1007/s00125-005-1760-0
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发表时间：
2005-06-01
期刊：
影响因子：
8.2
通讯作者：
Dullaart, RPF
中科院分区：
文献类型：
--
作者：
de Vries, R;Kerstens, MN;Dullaart, RPF
1型糖尿病患者细胞胆固醇向血浆外排在胆固醇逆向转运中起重要作用，并可能受辛伐他汀的影响。在14名中度高胆固醇血症的1型糖尿病患者和13名健康男性中，我们测定了血浆（载脂蛋白）、β - HDL前期形成、胆固醇酯转移蛋白（CETP）活性、磷脂转移蛋白（PLTP）活性、胆固醇酯化、胆固醇酯转移以及血浆诱导胆固醇流出Fu5AH细胞和成纤维细胞的能力。在饮食磨合后，糖尿病患者在双盲交叉设计中随机接受辛伐他汀10、20、40 mg和安慰剂治疗，每天一次，持续6周。糖尿病患者血浆极低密度脂蛋白(VLDL)+LDL胆固醇、LDL胆固醇、HDL磷脂、载脂蛋白（apo） A-I、载脂蛋白B、CETP活性、PLTP活性、胆固醇酯化、胆固醇酯转移以及血浆诱导Fu5AH细胞和成纤维细胞胆固醇外排的能力均较高。前- β - HDL的形成没有改变。辛伐他汀治疗可降低VLDL+LDL胆固醇、LDL胆固醇、甘油三酯和载脂蛋白B、CETP活性、胆固醇酯化和胆固醇酯转移。高密度脂蛋白胆固醇升高，其变化与胆固醇酯转移的变化相关。辛伐他汀后，促进Fu5AH细胞和成纤维细胞胆固醇外排的能力没有改变。中度高胆固醇血症型1型糖尿病患者血浆诱导胆固醇从Fu5AH细胞和成纤维细胞外排的能力增强，可能是由于较高的载脂蛋白A-I、HDL磷脂和PLTP活性。辛伐他汀通过降低血浆胆固醇酯转移而增加1型糖尿病患者的高密度脂蛋白胆固醇。辛伐他汀后HDL的改变不会进一步增加细胞胆固醇外排。
Cellular cholesterol efflux to plasma is important in reverse cholesterol transport and may be affected by simvastatin in type 1 diabetes mellitus. In 14 moderately hypercholesterolaemic type 1 diabetic and 13 healthy men we determined plasma (apo)lipoproteins, pre-beta HDL formation, cholesteryl ester transfer protein (CETP) activity, phospholipid transfer protein (PLTP) activity, cholesterol esterification, cholesteryl ester transfer and the capacity of plasma to induce cholesterol efflux out of Fu5AH cells and fibroblasts. After diet run-in, diabetic patients were randomly treated with simvastatin 10, 20, 40 mg and placebo, once daily each, for 6 weeks in a double-blind crossover design. Plasma very low density lipid protein (VLDL)+LDL cholesterol, LDL cholesterol, HDL phospholipids, apolipoprotein (apo) A-I, apo B, CETP activity, PLTP activity, cholesterol esterification, cholesteryl ester transfer and the capacity of plasma to induce cholesterol efflux from Fu5AH cells and fibroblasts were higher in diabetic patients. Pre-beta HDL formation was unaltered. Simvastatin treatment decreased VLDL+LDL cholesterol, LDL cholesterol, triglycerides and apo B, CETP activity, cholesterol esterification and cholesteryl ester transfer. HDL cholesterol increased and its change was correlated with the change in cholesteryl ester transfer. The ability to promote cholesterol efflux from Fu5AH cells and fibroblasts did not change after simvastatin. The capacity of plasma from moderately hypercholesterolaemic type 1 diabetic patients to induce cholesterol efflux out of Fu5AH cells and fibroblasts is enhanced, probably due to higher apo A-I, HDL phospholipids and PLTP activity. Simvastatin increases HDL cholesterol in type 1 diabetic patients via lowering of plasma cholesteryl ester transfer. The HDL changes after simvastatin do not increase cellular cholesterol efflux further.