Original Article

Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects

Correspondence to: Jeffrey S. Cohn

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, R., M. Tremblay, P. H. R. Barrett, H. Jacques, A. Fredenrich, O. Mamer, J. Davignon, and J. S. Cohn. Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects. J. Lipid Res. 2000. 41: 706;–718.

Supplementary key words: triglyceride, cholesterol, atherosclerosis, type III hyperlipoproteinemia, remnants, stable isotope, metabolism, apoB

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