Charge-based heterogeneity of human plasma lipoproteins at hypertriglyceridemia: capillary isotachophoresis study

To reveal the metabolic links between and within pools of pro-atherogenic triglyceride(TG)-rich lipoproteins and anti-atherogenic high density lipoproteins (HDL), the changes in lipoprotein profile at hypertriglyceridemia were analyzed by capillary isotachophoresis. Plasma samples from patients with apoE3/3 phenotype were stained with a fluorescent probe NBD-C6-ceramide and lipoproteins resolved into six H-, one (V+I) and four L-components which belong to HDL, very low and intermediate density (VLDL+IDL) and low density lipoproteins (LDL), respectively. The expected correlation between the relative size of the combined fractions and lipid and apolipoprotein values was obtained confirming the validity of the approach. The new findings were obtained as follows. (1) The fast L-component correlated inversely with HDL-cholesterol (Chol), while intermediate and slow H-components correlated inversely with plasma and LDL-Chol and apoB. (2) The content of intermediate and slow H-components increased within H-pool and decreased relative TG-rich lipoproteins as hypertriglyceridemia rose due to the impairment of triglyceride hydrolysis by lipoprotein lipase within TG-rich particles. (3) A predictive value of the ratios of fast to slow H-components as an indicator of lecithin:cholesterol acyltransferase activity was demonstrated which tended to decrease at hypertriglyceridemia. (4) The L1/L2 ratio may be considered as an indicator of the accumulation of small dense LDL, which is a feature of clinically manifested atherogenic B-pattern. The competition between H(DL) and L(DL) particles for hepatic lipase and significant contribution of apoE to functional deficiency of H(DL) particles at hypertriglyceridemia are suggested.