MECHANISMS OF HDL REDUCTION AFTER PROBUCOL - CHANGES IN HDL SUBFRACTIONS AND INCREASED REVERSE CHOLESTERYL ESTER TRANSFER
MECHANISMS OF HDL REDUCTION AFTER PROBUCOL - CHANGES IN HDL SUBFRACTIONS AND INCREASED REVERSE CHOLESTERYL ESTER TRANSFER
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DOI：
10.1161/01.atv.9.4.462
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发表时间：
1989-07-01
期刊：
影响因子：
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通讯作者：
SIRTORI, CR
中科院分区：
文献类型：
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作者：
FRANCESCHINI, G;SIRTORI, M;SIRTORI, CR
用普罗布考（一种广泛使用的降脂剂）治疗与高密度脂蛋白（HDL）胆固醇水平的显著降低有关，但与从组织中清除胆固醇酯的明显改善有关（例如，肌腱黄色瘤）。在安慰剂对照交叉试验后，在12名稳定型II型高脂血症[低密度脂蛋白（LDL）胆固醇> 180 mg/dl]患者中检测了普罗布考（500 mg，每日2次）对HDL亚组分分布和胆固醇酯转移活性的影响。普罗布考显著降低总胆固醇（-13.8%）、LDL胆固醇（-9.1%）和HDL胆固醇（-30%）。通过速率分区超离心，显示HDL 2胆固醇显著降低（-68%），而HDL 3的变化不太显著（-21%）。这些发现通过聚丙烯酰胺梯度凝胶电泳得到证实，通常显示HDL 2b颗粒减少或消失，HDL 3a范围内的颗粒普遍存在。胆固醇酯从高密度脂蛋白转移到低密度脂蛋白显着增加（30%），在所有患者。这些发现表明，除了在体外的变化（防止LDL过氧化和巨噬细胞摄取），普罗布考特征性地修改HDL颗粒分布在体内，并与胆固醇酯转移活性的显着增加。
Treatment with probucol, a widely used lipid-lowering agent, is associated with a significant reduction of high density lipoprotein (HDL) cholesterol levels, but with an apparently improved removal of cholesteryl esters from tissues (e.g., from tendon xanthomas). The effects of probucol (500 mg twice daily) on HDL subfraction distribution and cholesteryl ester transfer activity were tested in 12 patients with stable type II hyperlipidemia [low density lipoprotein (LDL) cholesterol > 180 mg/dl] after a placebo-controlled cross-over trial. Probucol significantly lowered total cholesterol (-13.8%) , LDL cholesterol (-9.1%), and HDL cholesterol (-30%). By rate zonal ultracentrifugation, a marked reduction of HDL2 cholesterol (-68%) was shown, whereas changes in HDL3 were less significant (-21%). These findings were confirmed by polyacrylamide gradient gel electrophoresis, typically showing a reduction or disappearance of HDL2b particles and the prevalence of particles in the HDL3a range. Cholesteryl ester transfer from HDL to lower density lipoproteins was significantly increased (30%) in all patients. These findings suggest that, in addition to the well-documented in vitro changes (prevention of LDL peroxidation and macrophage uptake), probucol characteristically modifies HDL particle distribution in vivo, and is associated with a significant increase of cholesteryl ester transfer activity.