Plasma concentration of apolipoprotein E in intermediate-sized remnant-like lipoproteins in normolipidemic and hyperlipidemic subjects.
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 +/- 0.11 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.
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Quebec, Canada.
J S
JS
Cohn
M
M
Tremblay
M
M
Amiot
D
D
Bouthillier
M
M
Roy
J
J
Genest
J
J
Davignon
D000328:Adult; D001057:Apolipoproteins E / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D006938:Hyperlipoproteinemia Type II / Q000097:blood; D006952:Hyperlipoproteinemia Type III / Q000097:blood; D006953:Hyperlipoproteinemia Type IV / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol