Journal of Lipid Research, Vol 25, 593-603, Copyright © 1984 by Lipid Research, Inc.
Effects of high cholesterol diets on rat plasma lipoproteins and lipoprotein-cell interactions
TG Cole, I Kuisk, W Patsch and G Schonfeld
High fat, high cholesterol diets do not produce atherosclerotic lesions in
some animal species such as the rat; however, when combined with
experimentally induced hypothyroidism, such diets do produce lesions. While
the diets or hypothyroidism each induce significant alterations in plasma
lipoproteins, the combination produces marked hypercholesterolemia. If the
atherosclerosis is related to the hyperlipidemia, the combination regimen
could be provoking changes in the structure or compositions of lipoproteins
which are not noted with either regimen alone. To test this hypothesis,
Sprague-Dawley male rats (approximately 250 g) were treated as follows:
Diet(a) = chow + 5% lard and 0.3% Na taurocholate; Diet(b) = Diet(a) + 2%
cholesterol; Diet(c) = Diet(b) + 0.1% propylthiouracil (PTU). The major
findings were as follows. 1) With Diet(b), slow floating very low density
lipoprotein (VLDL) (pre-beta) enriched in cholesteryl esters accumulated in
plasma and low density lipoprotein (LDL) disappeared from its usual
flotation position. 2) With Diet(c), changes in plasma concentration were
more marked but were also qualitatively different. More VLDL accumulated,
and distribution of VLDL was shifted toward even slower floating
cholesteryl ester-rich particles. VLDL had "broad beta" mobility. Also, a
beta-migrating intermediate density lipoprotein (IDL) population appeared.
3) Lipoprotein (d less than 1.019 g/ml) and zonal subfractions of d less
than 1.019 g/ml lipoproteins (isolated from rats on cholesterol Diet (b]
stimulated [3H]oleate incorporation into cholesteryl esters of fibroblasts
and macrophages, while the d less than 1.019 g/ml fractions of 5% fat
(Diet(a]-fed rats did not. 4) The major finding of this study was that
identically prepared d less than 1.019 g/ml fractions of Chol + PTU-treated
rats (Diet(c] were approximately 2.5-fold more stimulatory than the
lipoproteins of cholesterol-fed rats. The results could not be explained by
differences in cholesterol contents of the cholesterol-rich lipoproteins,
but significant differences in the apoprotein compositions of the fraction
were found which could be important. The most active fractions had higher
apoBL/apoBS and apoE/apoC ratios than less active fractions. Thus, the
combination regimen of cholesterol and PTU produced changes in lipoprotein
structure and composition which enhanced the abilities of the lipoproteins
to interact with cells. The results suggest that analysis of
lipoprotein-cell interactions in vitro may be predictive of the atherogenic
potential of lipoproteins in vivo and that euthyroidism in rat protects
against atherogenic hyperlipidemia.
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