Intravenous infusion of apolipoprotein E accelerates clearance of plasma lipoproteins in rabbits.
Plasma cholesterol levels in cholesterol-fed rabbits were markedly reduced by the intravenous infusion or bolus injection of recombinant human apo E or rabbit plasma apo E. Administration of 6-70 mg of apo E resulted in an approximately 20-40% acute reduction in plasma cholesterol levels within 2-3 h. Plasma cholesterol levels remained reduced for 4-8 h after the administration of apo E. Furthermore, the intravenous injection of apo E reduced the plasma cholesterol levels in Watanabe heritable hyperlipidemic rabbits. The addition of apo E to [14C]cholesterol-labeled canine thoracic duct lymph or [14C]cholesterol-labeled chylomicrons resulted in accelerated plasma clearance of these diet-induced lipoproteins in normal rabbits, with the uptake occurring primarily in the liver. This study suggests that the amount or availability of apo E in the plasma of cholesterol-fed rabbits may be rate limiting for the normal clearance of diet-induced remnant lipoproteins.
Mahley
R W
RW
Gladstone Foundation Laboratories for Cardiovascular Disease, University of California, San Francisco 94140.
Weisgraber
K H
KH
Hussain
M M
MM
Greenman
B
B
Fisher
M
M
Vogel
T
T
Gorecki
M
M
D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000493:pharmacokinetics*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002914:Chylomicrons / Q000378:metabolism; D004285:Dogs; D006937:Hypercholesterolemia / Q000097:blood; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008657:Metabolic Clearance Rate; D011817:Rabbits; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D012965:Sodium Chloride / Q000008:administration & dosage
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D002914:Chylomicrons; D008074:Lipoproteins; D011994:Recombinant Proteins; D012965:Sodium Chloride