Patients with nephrotic-range proteinuria have apolipoprotein C and E deficient VLDL1
Patients with nephrotic-range proteinuria have apolipoprotein C and E deficient VLDL1
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DOI：
10.1046/j.1523-1755.2000.00278.x
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发表时间：
2000-09-01
影响因子：
19.6
通讯作者：
Packard, CJ
中科院分区：
文献类型：
--
作者：
Deighan, CJ;Caslake, MJ;Packard, CJ
背景极低密度脂蛋白（VLDL）清除受损可导致肾病范围蛋白尿的血脂异常。VLDL可以细分为大的轻VLDL 1（S-1 60至400）和更小，更密集的VLDL 2（Sr 20至60）。在肾病范围的蛋白尿中，VLDL 1的清除延迟。VLDL 1脂解受载脂蛋白CII（apoCII）和apoCIII的影响，而apoE调节受体介导的清除。为了确定VLDL 1清除受损是否与VLDL 1载脂蛋白缺乏有关，我们检测了27例尿白蛋白>2 g/24 h沿着的肾小球疾病患者的VLDL亚组分浓度和VLDL 1载脂蛋白及脂质成分，以及27例年龄和性别匹配的对照。蛋白尿患者血浆VLDL 1、VLDL 2、apoC Ⅱ、apoC Ⅲ浓度升高（P均< 0.001），apoE浓度升高（P < 0.002）。患者似乎具有较小的VLDL 1颗粒，如通过每个颗粒的甘油三酯（中位数+四分位数间距，每个VLDL 1颗粒的摩尔数）评估的：患者，4.9（3.0至7.9）x 10（3）：对照，7.0（4.6至15.7）x 10（3），P < 0.05。apoCII降低，4.2（3.1至8.2）对比9.9（7.4 ~ 23.2），P < 0.0004;载脂蛋白C Ⅲ 16.6（9.1 ~ 27.2）对29.3（18.5 ~ 69.4），P < 0.02，载脂蛋白E含量0.17（0.08 ~ 0.44）对0.48（0.31 ~ 1.31），P < 0.006。蛋白尿患者VLDL 1表面游离胆固醇与磷脂比值升高（0.55 +/- 0.17 vs. 0.40 +/- 0.18，P < 0.002）。均为平均值+/- SD）。对于所有患者，VLDL 1 apoCII、apoCIII和apoE/颗粒含量与颗粒大小相关（apoCII，r（2）= 61.5%，P < 0.001：apoCIII。与游离胆固醇/磷脂比值呈负相关（apoCII，r（2）= 41.6%，P < 0.001; apoCIII，r（2）= 38.8%，P <0.001; apoE，r（2）= 11.7%，P < 0.05）。多变量分析表明，患者VLDL 1中apoCII和apoCIII的相对缺乏与较小的颗粒尺寸和游离胆固醇：磷脂（FC：PL）比增加有关。VLDL 1的载脂蛋白E含量与粒径有关，而与游离胆固醇无关。我们推测肾病范围蛋白尿中VLDL 1清除受损是由于apoCII、apoCIII和apoE缺乏的颗粒的出现。VLDL 1 apoC缺乏与形成具有高FC：PL比的较小颗粒相关，并且可能导致低效的脂解。VLDL 1 apoE缺陷与较小的VLDL 1颗粒相关，但与VLDL 1表面脂质含量无关，可能会降低受体介导的该脂蛋白清除率。
Background. Impaired very low-density lipoprotein (VLDL) clearance contributes to dyslipidemia in nephrotic-range proteinuria. VLDL can be subdivided into large light VLDL1 (S-1 60 to 400) and smaller, denser VLDL2 (Sr 20 to 60). In nephrotic-range proteinuria, the clearance of VLDL1 is delayed. VLDL1 lipolysis is influenced by apolipoprotein CII (apoCII) and apoCIII, whereas apoE regulates receptor-mediated clearance.Methods. To ascertain whether impaired VLDL1 clearance was related to a deficiency in apolipoproteins on VLDL1, we measured VLDL subfraction concentrations and VLDL1 apolipoprotein and lipid compositions in 27 patients with glomerular disease and urinary albumin >2 g/24 h along with 27 age- and sex-matched controls.Results. Proteinuric patients had increased plasma VLDL1, VLDL2, apoCII, apoCIII (all P < 0.001), and apoE concentration (P < 0.002). Patients appeared to have smaller VLDL1 particles, as assessed by triglyceride per particle (median + interquartile range, moles per VLDL1 particle): patients, 4.9 (3.0 to 7.9) x 10(3): controls, 7.0 (4.6 to 15.7) x 10(3), P < 0.05. with reduced apoCII, 4.2 (3.1 to 8.2) versus 9.9 (7.4 to 23.2), P < 0.0004; apoCIII, 16.6 (9.1 to 27.2) versus 29.3 (18.5 to 69.4), P < 0.02, and apoE content, 0.17 (0.08 to 0.44) versus 0.48 (0.31 to 1.31), P < 0.006. The VLDL1 surface free cholesterol to phospholipid results were increased in proteinuric patients (0.55 +/- 0.17 vs. 0.40 +/- 0.18, P < 0.002. all mean +/- SD). For all patients, VLDL1 apoCII, apoCIII, and apoE contents per particle were related to particle size (apoCII, r(2) = 61.5%, P < 0.001: apoCIII. r(2) = 75.8%, P < 0.001; apoE, r(2) = 58.2%, P < 0.001) and inversely to the free cholesterol to phospholipid ratio (apoCII, r(2) = 41.6%, P < 0.001; apoCIII, r(2) = 38.8%, P < 0.001; apoE, r(2) = 11.7%, P < 0.05). Multivariate analysis suggested that the relative lack of apoCII and apoCIII on patients VLDL1 was related to smaller particle size and increased free cholesterol:phospholipid (FC:PL) ratio. Particle size but not free cholesterol determined the apoE content of VLDL1.Conclusions. We postulate that impaired VLDL1 clearance in nephrotic-range proteinuria results from the appearance of particles deficient in apoCII, apoCIII, and apoE. VLDL1 apoC deficiency is associated with the formation of smaller particles with a high FC:PL ratio, and is likely to cause inefficient lipolysis. VLDL1 apoE deficiency is associated with smaller VLDL1 particles but not altered VLDL1 surface lipid content, and may reduce receptor-mediated clearance of this lipoprotein.