Lipoproteins Containing Apolipoprotein A-IV but Not Apolipoprotein A-I Take Up and Esterify Cell-Derived Cholesterol in Plasma

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Abstract
Two-dimensional nondenaturing polyacrylamide gradient gel electrophoresis (2D-PAGGE) identifies distinct apoA-I– or apoE-containing subclasses of high-density lipoproteins (HDLs), each of which plays a different role in reverse cholesterol transport. In this study we used 2D-PAGGE to investigate the role of apoA-IV–containing lipoproteins in reverse cholesterol transport in native plasma. Incubation of 2D electrophoretograms with anti–apoA-IV antibodies identified up to three subclasses of particles. The smaller particle subclasses, LpA-IV-1 and LpA-IV-2, were found in every plasma sample. The largest particle subclass, LpA-IV-3, was observed in fewer than 10% of the plasmas analyzed. 2D-PAGGE of apoA-I–deficient plasma and apoA-I–depleted plasma and anti–apoA-I immunosubtracting 2D-PAGGE of normal plasma revealed that LpA-IV-1 and LpA-IV-2 do not contain apoA-I. The importance of LpA-IV-1 and LpA-IV-2 for uptake and esterification of cell-derived cholesterol was investigated using pulse-chase incubations of plasma with [ 3 H]cholesterol-labeled fibroblasts followed by anti–apoA-I immunosubtracting 2D-PAGGE. During 1-minute pulse incubation with cells, [ 3 H]cholesterol was taken up by γ-LpE >LpA-IV-1 >pre-β 1 -LpA-I >LpA-IV-2 (“>” denotes “more than”). During subsequent chase incubation without cells, proportionately less radioactivity disappeared from LpA-IV-1 and LpA-IV-2 than from pre-β 1 -LpA-I and γ-LpE. During 5-minute pulse incubations, radioactive cholesteryl esters were formed in pre-β 3 -LpA-I >α-LpA-I >LpA-IV-1 >LpA-IV-2. The fractional esterification rate was highest in pre-β 3 -LpA-I and lowest in α-LpA-I. Subsequent chase led to the disappearance of [ 3 H]cholesteryl esters from pre-β 3 -LpA-I and, to a lesser extent, from LpA-IV-1 and LpA-IV-2 but to an increase of [ 3 H]cholesteryl esters in α-LpA-I and LDL. Similar pulse-chase experiments with apoA-I–deficient plasma revealed that LpA-IV-1 and LpA-IV-2 take up and esterify cell-derived cholesterol even more effectively than in normal plasma. We conclude that LpA-IV-1 and LpA-IV-2 are apoA-I–free lipoproteins that are important contributors to reverse cholesterol transport.

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