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首页> 外文期刊>Journal of Medical Biochemistry >Serum sdLDL-C and Cellular SREBP2-dependent Cholesterol Levels; is there a Challenge on Targeting PCSK9?
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Serum sdLDL-C and Cellular SREBP2-dependent Cholesterol Levels; is there a Challenge on Targeting PCSK9?

机译：血清sdLDL-C和细胞SREBP2依赖性胆固醇水平;以PCSK9为目标有挑战吗？

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Summary Background Serum small dense LDL-cholesterol (sdLDL-C) value is suggested to bean important risk factor for atherosclerosis. Since sdLDL-C changes may be related to PCSK9 and SREBP-2 functions, the aim of this study was to investigate correlations between sdLDL-C, circulating PCSK9, SREBP-2 expression and some lipid parameters in serum and butty coat fraction of healthy subjects. Methods One hundred and twenty-four subjects were randomly included in the study. The lipid profile was measured using routine laboratory methods. The serum sdLDL-C level was calculated by a heparin-related precipitation technique. The cellular LDL-C/protein and cholesterol/protein values were measured after lysing of cells with methanol/chloroform binary solvent. The circulating PCSK9 level was measured using ELISA technique. The SREBP-2 expression level was estimated using theRT-qPCR technique. Results Data showed significant correlations between LDL-C, TG and sdLDL-C levels (r=0.34, p=0.001; r=0.2, p=0.04). The circulating PCSK9 level was correlated to LDL-C (r=0.29, p=0.04), but not to sdLDL-C (r=-0.08, p=0.57). Also, cellular LDL-C value was not related to serum LDL-C level (r=-0.12, p=0.39). Furthermore, there was an inverse correlation between cellular LDL-C/protein value and estimated de novo cholesterol/protein value (r= -0.5, p=0.001). Similar results were observed for cellular LDL-C/protein value and SREBP-2 expression level (r= -0.52, p=0.004). Conclusions We concluded that the serum sdLDL-C value is not related to circulating PCSK9. Furthermore, SREBP-2 regulatory system was able to elevate the cellular cholesterol level after reducing LDL influx. We suggest to investigate the cellular sdLDL fate and lipid synthesis pathways in PCSK9-targeting studies.
机译：发明背景血清小浓度低密度脂蛋白胆固醇（sdLDL-C）值被认为是动脉粥样硬化的重要危险因素。由于sdLDL-C的变化可能与PCSK9和SREBP-2的功能有关，因此本研究的目的是研究健康受试者的血清和臀部部分中sdLDL-C，循环PCSK9，SREBP-2表达与某些脂质参数之间的相关性。 。方法将124名受试者随机纳入研究。使用常规实验室方法测量脂质分布。通过肝素相关沉淀技术计算血清sdLDL-C水平。在用甲醇/氯仿二元溶剂裂解细胞后，测量细胞的LDL-C /蛋白质和胆固醇/蛋白质值。使用ELISA技术测量循环的PCSK9水平。使用RT-qPCR技术估计SREBP-2表达水平。结果数据显示LDL-C，TG和sdLDL-C水平之间存在显着相关性（r = 0.34，p = 0.001; r ​​= 0.2，p = 0.04）。循环PCSK9水平与LDL-C相关（r = 0.29，p = 0.04），但与sdLDL-C不相关（r = -0.08，p = 0.57）。另外，细胞LDL-C值与血清LDL-C水平无关（r ＝ -0.12，p ＝ 0.39）。此外，细胞LDL-C /蛋白质值与从头胆固醇/蛋白质估计值之间呈负相关（r = -0.5，p = 0.001）。对于细胞LDL-C /蛋白质值和SREBP-2表达水平，观察到相似的结果（r ＝ -0.52，p ＝ 0.004）。结论我们得出结论，血清sdLDL-C值与循环PCSK9无关。此外，SREBP-2调节系统在减少LDL流入后能够提高细胞胆固醇水平。我们建议在PCSK9靶向研究中研究细胞sdLDL的命运和脂质合成途径。

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