Articles |
From the Hyperlipidemia and Atherosclerosis Research Group and the Cardiovascular Genetics Laboratory (J.G.), Clinical Research Institute of Montreal, Quebec, Canada.
Correspondence to Dr J.S. Cohn, Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Ave W, Quebec, Canada, H2W 1R7.
Abstract Triglyceride-rich lipoprotein (TRL) remnants have been strongly implicated in the pathogenesis of atherosclerosis. To further investigate plasma remnant lipoprotein metabolism, we have determined the plasma concentration of apolipoprotein (apo) E (by polyclonal enzyme-linked immunoassay) in remnant-like lipoproteins, isolated by automated gel filtration chromatography as a fraction intermediate in size between VLDL and HDL. In normolipidemic subjects (n=12), 1.2±0.1 mg/dL (33±2%, mean±SE) of total plasma apoE was associated with this fraction (termed ISL apoE). In hypercholesterolemic (type IIa, n=12), hypertriglyceridemic (type IV, n=12), and mixed hyperlipidemic (type IIb, n=12) subjects, mean ISL apoE concentrations were 2.1±0.2, 2.5±0.2, and 3.8±0.4 mg/dL, respectively (P<.001 versus normal values) (45±2%, 32±2%, and 44±2% of total). ISL apoE was 8.7±1.4 mg/dL (42±3%) in type III dyslipidemic subjects (apoE2/2, n=8). ISL apoE was positively correlated with plasma triglyceride (r=.41, P<.01), and at any given level of plasma triglyceride, subjects with an apoE2/2 or apoE3/2 phenotype tended to have a higher concentration of ISL apoE (P<.01) than apoE3/3 or E4/3 individuals. ISL apoE was also correlated (P<.001) with total plasma cholesterol (r=.66), TRL cholesterol (r=.49), TRL apoE (r=.47), LDL apoB (r=.42), and LDL+HDL triglyceride (r=.74). These results suggest that (1) a significant proportion of plasma apoE resides within an intermediate-sized remnant-like lipoprotein fraction in both normolipidemic and hyperlipidemic subjects; (2) plasma remnant lipoprotein accumulation is associated with an elevation in ISL apoE concentration; and (3) ISL apoE concentration is significantly correlated with various proatherogenic lipid parameters and may itself be a potentially important atherogenic index.
Key Words: triglyceride-rich lipoproteins apoE phenotype FPLC atherosclerosis coronary artery disease
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