Lecithin: cholesterol acyltransfer, dyslipoproteinaemia and membrane lipids in uraemia

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.