Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects.
Apolipoprotein (apo) C-III and apoE play a central role in controlling the plasma metabolism of triglyceride-rich lipoproteins (TRL). We have investigated the plasma kinetics of total, very low density lipoprotein (VLDL) and high density lipoprotein (HDL) apoC-III and apoE in normolipidemic (NL) (n = 5), hypertriglyceridemic (HTG, n = 5), and Type III hyperlipoproteinemic (n = 2) individuals. Apolipoprotein kinetics were investigated using a primed constant (12 h) infusion of deuterium-labeled leucine. HTG and Type III patients had reduced rates of VLDL apoB-100 catabolism and no evidence of VLDL apoB-100 overproduction. Elevated (3- to 12-fold) total plasma and VLDL apoC-III levels in HTG and Type III patients, although associated with reduced apoC-III catabolism (i.e., increased residence times (RTs)), were mainly due to increased apoC-III production (plasma apoC-III transport rates (TRs, mean +/- SEM): (NL) 2.05 +/- 0.22 (HTG) 4.90 +/- 0.81 (P < 0.01), and (Type III) 8.78 mg. kg(-)(1). d(-)(1); VLDL apoC-III TRs: (NL) 1.35 +/- 0. 23 (HTG) 5.35 +/- 0.85 (P < 0.01), and (Type III) 7.40 mg. kg(-)(1). d(-)(1)). Elevated total plasma and VLDL apoE levels in HTG (2- and 6-fold, respectively) and in Type III (9- and 43-fold) patients were associated with increased VLDL apoE RTs (0.21 +/- 0.02, 0.46 +/- 0. 05 (P < 0.01), and 1.21 days, NL vs. HTG vs. Type III, respectively), as well as significantly increased apoE TRs (plasma: (NL) 2.94 +/- 0.78 (HTG) 5.80 +/- 0.59 (P < 0.01) and (Type III) 11.80 mg. kg(-)(1). d(-)(1); VLDL: (NL) 1.59 +/- 0.18 (HTG) 4.52 +/- 0.61 (P < 0.01) and (Type III) 11.95 mg. kg(-)(1). d(-)(1)). These results demonstrate that hypertriglyceridemic patients, having reduced VLDL apoB-100 catabolism (including patients with type III hyperlipoproteinemia) are characterized by overproduction of plasma and VLDL apoC-III and apoE.
Batal
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Hyperlipidemia and Atherosclerosis Research Group, Montréal, Québec, Canada H2W 1R7.
Tremblay
M
M
Barrett
P H
PH
Jacques
H
H
Fredenrich
A
A
Mamer
O
O
Davignon
J
J
Cohn
J S
JS
D000328:Adult; D053299:Apolipoprotein B-100; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000097:blood; D001056:Apolipoproteins C / Q000097:blood*; D001057:Apolipoproteins E / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D053299:Apolipoprotein B-100; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides