ApoE enhances lipid uptake by macrophages in lipoprotein lipase deficiency during pregnancy

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.