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Journal of Lipid Research, Vol 33, 1807-1816, Copyright © 1992 by Lipid Research, Inc.
ST Kunitake, CM Mendel and LK Hennessy
Apolipoprotein (apo) A-I-containing lipoproteins can be separated into two
subfractions, pre-beta HDL and alpha HDL (high density lipoproteins), based
on differences in their electrophoretic mobility. In this report we present
results indicating that these two subfractions are metabolically linked.
When plasma was incubated for 2 h at 37 degrees C, apoA-I mass with
pre-beta electrophoretic mobility disappeared. This shift in apoA-I mass to
alpha electrophoretic mobility was blocked by the addition of either 1.4 mM
DTNB or 10 mM menthol to the plasma prior to incubation, suggesting that
lecithin:cholesterol acyltransferase (LCAT) activity was involved. There
was no change in the electrophoretic mobility of either pre-beta HDL or
alpha HDL when they were incubated with cholesterol-loaded fibroblasts.
However, after exposure to the fibroblasts, the cholesterol content of the
pre-beta HDL did increase approximately sixfold, suggesting that pre-beta
HDL can associate with appreciable amounts of cellular cholesterol.
Pre-beta HDL-like particles appear to be generated by the incubation of
alpha HDL with cholesteryl ester transfer protein (CETP) and either very
low density lipoproteins (VLDL) or low density lipoproteins (LDL). This
generation of pre-beta HDL-like particles was documented both by
immunoelectrophoresis and by molecular sieve chromatography. Based on these
findings, we propose a cyclical model in which 1) apoA-I mass moves from
pre-beta HDL to alpha HDL in connection with the action of LCAT and the
generation of cholesteryl esters within the HDL, and 2) apoA-I moves from
alpha HDL to pre-beta HDL in connection with the action of CETP and the
movement of cholesteryl esters out of the HDL. Additionally, we propose
that the relative plasma concentrations of pre-beta HDL and alpha HDL
reflect the movement of cholesteryl esters through the HDL. Conditions that
result in the accumulation of HDL cholesteryl esters will be associated
with low concentrations of pre-beta HDL, whereas conditions that result in
the depletion of HDL cholesteryl esters will be associated with elevated
concentrations of pre-beta HDL. This postulate is consistent with published
findings in patients with hypertriglyceridemia and LCAT deficiency.
ARTICLES
Interconversion between apolipoprotein A-I-containing lipoproteins of pre-beta and alpha electrophoretic mobilities
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
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