High density lipoproteins (HDL) can be separated into distinct particles based on apolipoprotein (apo) content. The present study compares the in vivo metabolism of the apoE-containing HDL particles LpE, LpE:A-I and LpE:A-I:A-II. The particles were purified from plasma by immunoaffinity chromatography and had alpha-mobility on agarose and 2D gel electrophoresis. The cholesteryl ester/free cholesterol and phospholipid/total cholesterol ratios in the apoE-containing particles were 0.7 and 1.0 for LpE, 1.4 and 1.1 for LpE:A-I, and 1.8 and 1.2 for LpE:A-I:A-II, respectively. Radiolabeled apoE was reassociated with the particles and the particles were injected into normolipidemic volunteers: 125I-LpE and 131I-LpE:A-I:A-II (n=3), 125I-LpE:A-I and 131I-LpE:A-I:A-II (n=3) and 125I-LpE and 131I-LpE:A-I (n=2). Fractional catabolic rates (FCR) for LpE, LpE:A-I and LpE:A-I:A-II were 3.4""""""""0.4d-1, 3.1""""""""0.3d-1 and 2.7""""""""0.4d-1, respectively (p=0.01 for LpE vs. LpE:A-I:A-II). The apoE-containing HDL particles were catabolized much more rapidly than are apoA-containing HDL particles, LpA-I (FCR 0.232d-1) and LpA-I:A-II (FCR 0.195d-1). Immunoaffinity chromatography showed that LpE:A-I particles were converted to LpE:A-I:A-II particles, whereas there was no apparent metabolic conversion of LpE and LpE:A-I:A-II. FPLC and ultracentrifugation analyses revealed that after injection there was a decrease in the percentage of radioactivity in HDL and an increase in VLDL, for up to 8 hours, coinciding with the post-prandial state of the subjects. At later timepoints the proportion of radioactivity in HDL increased. In conclusion: 1) ApoE-containing HDL particles are catabolized more rapidly than apoA-containing HDL, with LpE>LpE:A-I>LpE:A-I:A-II >> LpA-I>LpA-I:A-II. 2) The presence of apoE dramatically changes the metabolic pathways of lipoprotein particles within HDL.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL002056-02
Application #
6162695
Study Section
Special Emphasis Panel (MDB)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code