Effects of high-density lipoprotein particles containing apo A-I, with or without apo A-II, on intracellular cholesterol efflux.
Previous reports have shown a differential effect of high-density lipoprotein (HDL) particles which contain apolipoprotein (apo) A-I without apo A-II (Lp A-I) and particles containing both apo A-I and apo A-II (Lp A-I/A-II) on cholesterol efflux from the mouse adipocyte cell line Ob1771, with Lp A-I and Lp A-I/A-II being active and inactive cholesterol efflux promotors, respectively. The present study was conducted to examine the roles of these two populations of apo-specific HDL particles on reverse cholesterol transport from cholesterol-loaded human skin fibroblasts and bovine aortic endothelial cells. The ability of HDL particles to remove intracellular cholesterol was tested by measuring depletion of the substrate pool for acylCoA:cholesterol acyltransferase (ACAT) and efflux of newly synthesized cholesterol, while removal of plasma membrane cholesterol was assessed by measuring efflux of [3H]cholesterol from prelabeled cells. Lp A-I and Lp A-I/A-II isolated from HDL2, HDL3 or plasma by immunoaffinity techniques each decreased esterification of cholesterol by both fibroblasts and endothelial cells. A mixture of Lp A-I and Lp A-I/A-II isolated from HDL3 decreased cholesterol esterification by fibroblasts in an additive manner, thus demonstrating that Lp A-I/A-II did not inhibit Lp A-I-mediated cholesterol efflux. Both Lp A-I and Lp A-I/A-II promoted efflux of sterol newly synthesized by fibroblasts, and no significant differences were observed between the apo-specific particles. Apo-specific particles were also similarly effective at preventing the accumulation of LDL-derived cholesterol in cholesterol-depleted fibroblasts. Efflux of [3H]cholesterol from plasma membranes was stimulated to similar extents by Lp A-I and Lp A-I/A-II isolated from either HDL2, HDL3 or plasma. Thus, the apo-specific HDL particles Lp A-I and Lp A-I/A-II are both effective promoters of cholesterol efflux from fibroblasts and aortic endothelial cells.
Oikawa
S
S
Department of Medicine, University of Washington, Seattle.
Mendez
A J
AJ
Oram
J F
JF
Bierman
E L
EL
Cheung
M C
MC
D000818:Animals; D016632:Apolipoprotein A-I / Q000302:isolation & purification* / Q000494:pharmacology; D016633:Apolipoprotein A-II / Q000302:isolation & purification* / Q000494:pharmacology; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000096:biosynthesis; D004730:Endothelium, Vascular; D005347:Fibroblasts; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D002784:Cholesterol