Gillett M P, Obineche E N, El-Rokhaimi M, Lakhani M S, Abdulle A, Sulaiman M
Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates.
J Nephrol. 2001 Nov-Dec;14(6):472-80.
Dyslipoproteinaemia is the most important complication linked to the increased morbidity and mortality of uraemic patients from cardiovascular disease. Many factors contribute to the dyslipoproteinaemia, including increased production of very low density lipoproteins (VLDL), decreased lipolysis and impaired low density lipoprotein (LDL) receptor activity. In this study, the role of decreased lecithin:cholesterol acyltransferase (LCAT) activity in relation to plasma and membrane lipid changes is examined.
Fasted blood samples were taken from 65 uraemic patients, including roughly equal numbers of haemodialysis, peritoneal dialysis and undialysed subjects, and from 29 apparently healthy individuals. Plasma total and free cholesterol, cholesteryl esters (CE), total and individual phospholipids, high density lipoprotein (HDL)-, LDL- and VLDL-cholesterol were all measured, as were erythrocyte and lymphocyte free cholesterol and phospholipids.
More than half of all patients, including those both on haemodialysis and peritoneal dialysis, as well as untreated individuals, had relative plasma concentrations of CE below the normal mean - 2SD. These patients had significantly decreased LDL- (2.62 +/- 1.04 compared to 3.61 +/- 0.97 mmol/L; p < 0.001) and HDL-cholesterol (0.71 +/- 0.30 compared to 0.94 +/- 0.27 mmol/L; p < 0.01) and increased VLDL-cholesterol (0.60 +/- 0.50 compared to 0.47 +/- 0.26 mmol/L; p < 0.05) as well as significant increases in membrane cholesterol and cholesterol/phospholipid molar ratio in erythrocytes (3.30 +/- 0.49 and 0.87 +/- 0.08 compared to 2.95 +/- 0.18 mmol/g wet weight and 0.76 +/- 0.04 mol/mol respectively, both p < 0.001) and cholesterol/phospholipid molar ratio of lymphocytes (0.58 +/- 0.14 compared to 0.45 +/- 0.04 mol/mol; p < 0.001). They were markedly deficient in LCAT activity (56.1 +/- 20.4 compared to 105.5 +/- 17.5 nmol/ml/h; p < 0.001). The LCAT activity in plasma of patients with high CE was higher than for those with low CE, but it was also significantly less than normal and this group showed smaller changes in other lipid parameters.
LCAT deficiency is common in uraemia and is associated with changes not just in plasma lipids, but also in membrane lipids which may be relevant to the progression of the disease.
血脂蛋白异常是与尿毒症患者心血管疾病发病率和死亡率增加相关的最重要并发症。许多因素导致血脂蛋白异常，包括极低密度脂蛋白（VLDL）生成增加、脂解作用降低以及低密度脂蛋白（LDL）受体活性受损。在本研究中，研究了卵磷脂胆固醇酰基转移酶（LCAT）活性降低与血浆和膜脂质变化的关系。
采集了65例尿毒症患者（包括数量大致相等的血液透析、腹膜透析和未透析患者）以及29例明显健康个体的空腹血样。检测了血浆总胆固醇和游离胆固醇、胆固醇酯（CE）、总磷脂和各磷脂、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和极低密度脂蛋白（VLDL）胆固醇，以及红细胞和淋巴细胞游离胆固醇和磷脂。
超过一半的患者，包括血液透析、腹膜透析患者以及未治疗患者，其血浆CE相对浓度低于正常均值减2个标准差。这些患者的LDL胆固醇（分别为2.62±1.04与3.61±0.97 mmol/L；p<0.001）和HDL胆固醇（分别为0.71±0.30与0.94±0.27 mmol/L；p<0.01）显著降低，VLDL胆固醇升高（分别为0.60±0.50与0.47±0.26 mmol/L；p<0.05），红细胞膜胆固醇和胆固醇/磷脂摩尔比显著增加（分别为3.30±0.49与2.95±0.18 mmol/g湿重，以及0.87±0.08与0.76±0.04 mol/mol，均p<0.001），淋巴细胞胆固醇/磷脂摩尔比也增加（分别为0.58±0.14与0.45±0.04 mol/mol；p<0.001）。他们的LCAT活性明显缺乏（分别为56.1±20.4与105.5±17.5 nmol/ml/h；p<0.001）。CE水平高的患者血浆LCAT活性高于CE水平低的患者，但仍显著低于正常水平，且该组其他脂质参数变化较小。
LCAT缺乏在尿毒症中很常见，不仅与血浆脂质变化有关，还与膜脂质变化有关，这可能与疾病进展相关。
