Accumulation of an apoE-poor subfraction of very low density lipoprotein in hypertriglyceridemic men.
Studies were undertaken to investigate the mechanism of the marked accumulation of an apoE-poor very low density lipoprotein (VLDL) subfraction in untreated Type IV and IIb hypertriglyceridemic subjects. Heparin-Sepharose chromatography was used to separate large VLDL (Sf 60-400) from fasted subjects, into an apoE-poor, unbound fraction and an apoE-rich, bound fraction. As a percent of total VLDL protein, the apoE-poor fraction comprised 40 +/- 4% of total VLDL in hypertriglyceridemic subjects versus 25% in normal subjects. Compared to the apoE-rich, bound fraction, this apoE-poor material was found to have a 5-fold lower ratio of apoE to apoC (0.20 +/- 0.06 vs 0.91 +/- 0.18, P less than 0.005), but a 1.5-fold higher ratio of triglyceride to protein (11.41 +/- 0.85 vs 7.97 +/- 0.77, P less than 0.01). In addition, the apoE-poor fraction was found to be enriched 2-fold in apoB-48 (10.30 +/- 2.41% vs 5.73 +/- 1.59% of total apoB, P less than 0.005) compared to the apoE-rich fraction, suggesting that the apoE-poor fraction contains more chylomicron remnants. The amount of this apoE-poor VLDL was markedly reduced following a reduction in VLDL triglyceride levels (a decrease from 40 +/- 4% to 21 +/- 2% of VLDL protein following a 50% reduction in VLDL triglyceride levels). The large VLDL from Type I, III, and V hyperlipoproteinemic subjects subfractionated using heparin-Sepharose showed an equal distribution of apoE between the two fractions in contrast with the Type IV and IIb subjects. The separation of VLDL from Type I, III, and V subjects using heparin-Sepharose involves a mechanism other than apoE binding. Separation in the latter likely results from apoB-100 binding to heparin, as opposed to apoE binding of VLDL from Type IV and IIb subjects.
Evans
A J
AJ
Department of Medicine, University of Western Ontario, London, Canada.
Huff
M W
MW
Wolfe
B M
BM
D001057:Apolipoproteins E / Q000097:blood*; D002846:Chromatography, Affinity; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000097:blood; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D006952:Hyperlipoproteinemia Type III / Q000097:blood; D006953:Hyperlipoproteinemia Type IV / Q000097:blood*; D006954:Hyperlipoproteinemia Type V / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000302:isolation & purification; D008297:Male; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride