The role of subfractions of high density lipoprotein in the in vivo transport of cholesterol from cholesterol-loaded hepatic and peripheral endothelial cells in the New Zealand white rabbit.
1. High density lipoprotein (HDL) of the New Zealand White rabbit was separated by heparin-Sepharose affinity chromatography into six distinct subfractions of different composition and particle size. 2. When human acetyl LDL containing [3H]cholesteryl linoleate was injected intravenously into rabbits to prime the endothelial cells with labelled cholesterol, only 1-2% of the radioactivity remained in the plasma after 2 hr. 3. After 4 hr, 60.1% of the plasma radioactivity was present in HDL and 25% of this was recovered in the largest particles of HDL (fraction VI, mean particle diameter 11.6-11.8 nm). 4. The concentration of these largest particles of HDL, rich in apolipoprotein E, were also relatively increased in acetyl-LDL-treated rabbits when compared to controls (P < 0.01). 5. In control in vitro experiments, 62.2% of the radioactivity recovered in HDL was associated with subfractions IV and V (mean particle diameter 10.2-10.8 nm) while only 5% was present in fraction VI. 6. The results show that large HDL particles enriched with apo E contain a large proportion of cholesterol previously supplied to hepatic and peripheral endothelial cells. 7. This study demonstrated that the rabbit provides a useful animal model for the study of the metabolism of subfractions of HDL in relation to reverse cholesterol transport.
Fragoso
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YD
Department of Molecular and Cell Biology, University of Aberdeen, Marischal College, U.K.
Skinner
E R
ER
D000818:Animals; D001011:Aorta; D001057:Apolipoproteins E / Q000032:analysis; D001692:Biological Transport; D005591:Chemical Fractionation; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002788:Cholesterol Esters / Q000008:administration & dosage; D002846:Chromatography, Affinity; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D010316:Particle Size; D011817:Rabbits
D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C032629:acetyl-LDL; C021976:cholesteryl linoleate; D002784:Cholesterol