Journal of Lipid Research, Vol 37, 972-984, Copyright © 1996 by Lipid Research, Inc.
ApoE enhances lipid uptake by macrophages in lipoprotein lipase deficiency during pregnancy
FM Steinberg, EC Tsai, JD Brunzell and A Chait
Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle 98195-6426, USA.
A woman with primary lipoprotein lipase (LPL) deficiency developed marked
hypertriglyceridemia, pancreatitis, eruptive xanthomas, and unusual palmar
xanthomas during pregnancy. Hypotheses to account for the palmar xanthomas
were that oxidative modification of triglyceride (TG)-rich lipoproteins
occurred due to increased plasma residence time, or that their
apolipoprotein E (apoE) content was abnormally elevated. Indices of
oxidation of her TG-rich lipoproteins did not support the hypothesis that
oxidative changes were a causative factor for her xanthomata. However,
degradation of her TG-rich lipoproteins by macrophages was markedly
increased (1844 ng/mg protein) during pregnancy as compared to
hypertriglyceridemic (with normal LPL) and normotriglyceridemic controls
(352 and 126 ng/mg protein, respectively). Post pregnancy the degradation
of the subject's TG-rich lipoproteins fell to 289 ng/mg protein.
Compositional analysis showed significant enrichment of the particles with
apoE (0.97 mass ratio of apoE:apoB during pregnancy, in contrast to 0.38
for normolipidemic controls), and was correlated with the rate of
degradation of the TG- rich lipoproteins. Thus, the increased uptake of the
TG-rich lipoproteins by macrophages appears to be the result of an unusual
enrichment of these lipoproteins with apoE.
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