Braschi S, Masson D, Rostoker G, Florentin E, Athias A, Martin C, Jacotot B, Gambert P, Lallemant C, Lagrost L
Service de Médecine V, Hôpital Henri Mondor, Créteil, France.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2559-67. doi: 10.1161/01.atv.17.11.2559.
Plasma cholesteryl ester transfer protein (CETP) activity, evaluated by the transfer of radiolabeled cholesteryl esters from a tracer dose of tritiated HDL to the plasma apolipoprotein B-containing lipoproteins, was significantly higher in patients with untreated idiopathic nephrotic syndrome (n = 15) than in normolipidemic control subjects (n = 22) (81.5 +/- 8.4 versus 43.1 +/- 3.1 micrograms CE.mL-1.h-1, respectively; P < .001). The increased CETP activity in nephrotic plasma was explained by a significant rise in both the CETP mass concentration (3.2 +/- 0.2 versus 2.1 +/- 0.1 mg/L; P < .001), and the specific CETP activity, calculated as the ratio of CETP activity to CETP mass (25.3 +/- 1.7 versus 20.4 +/- 1.6 micrograms CE.mg-1.h-1; P < .05). Elevated CETP activity in nephrotic patients was shown to be associated with a significant decrease in the mean size of LDL (24.4 +/- 0.5 versus 26.3 +/- 0.5 nm; P < .0001) as well as in the relative abundance of HDL2a (29.6 +/- 1.6% versus 34.8 +/- 1.1%; P < .05). The nephrotic syndrome was characterized by a significant increase in the relative proportion of lipoprotein-bound nonesterified fatty acids (NEFAs) (35.4 +/- 7.7% versus 7.6 +/- 3.0% of total; P < .01), leading to a significant increase in the electronegative charge of LDL (-4.3 +/- 0.1 versus -3.9 +/- 0.1 mV; P < .05) and HDL (-11.5 +/- 0.1 versus -11.1 +/- 0.2 mV; P < .05). Compared with native, non-supplemented plasma, removal of lipoprotein-bound NEFAs by addition of fatty acid-poor albumin to total plasma from nephrotic patients or control subjects significantly decreased CETP activity and specific CETP activity. Specific CETP activity no longer differed between nephrotic and control groups after albumin supplementation (19.7 +/- 1.5 versus 17.7 +/- 1.5 micrograms CE.mg-1.h-1; NS). It is concluded that, in addition to elevated CETP mass concentration, lipoprotein-bound NEFAs, by increasing the negative electrostatic charge of nephrotic lipoproteins, can facilitate the CETP-mediated neutral-lipid transfer reaction in total plasma from nephrotic patients.
通过将放射性标记的胆固醇酯从微量氚标记的高密度脂蛋白（HDL）转移至血浆中含载脂蛋白B的脂蛋白来评估血浆胆固醇酯转运蛋白（CETP）活性，结果显示，未经治疗的特发性肾病综合征患者（n = 15）的该活性显著高于血脂正常的对照受试者（n = 22）（分别为81.5±8.4与43.1±3.1微克胆固醇酯·毫升⁻¹·小时⁻¹；P <.001）。肾病患者血浆中CETP活性增加的原因是CETP质量浓度显著升高（3.2±0.2与2.1±0.1毫克/升；P <.001）以及比CETP活性（以CETP活性与CETP质量之比计算）显著升高（25.3±1.7与20.4±1.6微克胆固醇酯·毫克⁻¹·小时⁻¹；P <.05）。肾病患者中升高的CETP活性与低密度脂蛋白（LDL）平均大小显著减小（24.4±0.5与26.3±0.5纳米；P <.0001）以及HDL2a相对丰度显著降低（29.6±1.6%与34.8±1.1%；P <.05）相关。肾病综合征的特征是脂蛋白结合的非酯化脂肪酸（NEFA）相对比例显著增加（占总量的35.4±7.7%与7.6±3.0%；P <.01），导致LDL（-4.3±0.1与-3.9±0.1毫伏；P <.05）和HDL（-11.5±0.1与-11.1±0.2毫伏；P <.05）的负电荷显著增加。与天然的、未补充的血浆相比，向肾病患者或对照受试者的全血浆中添加低脂肪酸白蛋白以去除脂蛋白结合的NEFA，可显著降低CETP活性和比CETP活性。补充白蛋白后，肾病组与对照组之间的比CETP活性不再有差异（19.7±1.5与17.7±1.5微克胆固醇酯·毫克⁻¹·小时⁻¹；无显著性差异）。研究得出结论，除了CETP质量浓度升高外，脂蛋白结合的NEFA通过增加肾病患者血浆中脂蛋白的负静电荷，可促进CETP介导的中性脂质转移反应。
