In vivo cholesterol kinetics in apolipoprotein E-deficient and control mice.
The in vivo total body cholesterol transport of homozygous apoE-deficient (-/-) and control (+/+) mice was evaluated by compartmental analysis of plasma cholesterol decay. Body cholesterol fractional catabolic rates of chow fed mutants were less (-/-, 0.17 +/- 0.02; +/+, 0.51 +/- 0.06 day-1) and body cholesterol contents greater (-/-, 68 +/- 5; +/+, 48 +/- 5 mumol) than controls. The body cholesterol expansion of the chow-fed mutant was extracellular with at least half in plasma. Cholesterol transport, i.e., the mass entering, moving through, and exiting the body each day, was similar (-/-, 6.9 +/- 0.7; +/+, 8.5 +/- 0.9 mumol/day) for homozygotes and controls on chow, and both tripled with cholesterol feeding. Differing from controls, however, mutants had considerable expansions of plasma and body cholesterol (-/-, 166 +/- 21; +/+, 59 +/- 11 mumol) with increments in peripheral tissue cholesterol contents. Cholesterol feeding increased control hepatic cholesterol without a change in plasma, whereas mutants had large increments in plasma cholesterol with no change in liver. Consistent with impaired hepatic uptake of cholesterol, mutants had much slower plasma clearance of lipoprotein cholesterol, as well as slower transfer to catabolic pools than normals. Treatment of homozygotes with lovastatin doubled both plasma cholesterol concentration and body cholesterol transport indicating the importance of apoE-dependent cell cholesterol transfer in synthetic down-regulation with this agent. These data indicate that mice lacking apoE have lower affinity hepatic uptake of plasma remnant cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
Quarfordt
S H
SH
Department of Medicine, Durham VA Hospital, NC 27705, USA.
Oswald
B
B
Landis
B
B
Xu
H S
HS
Zhang
S H
SH
Maeda
N
N
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001692:Biological Transport; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005260:Female; D006720:Homozygote; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D051379:Mice
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D002784:Cholesterol; D008148:Lovastatin