Effect of the Apolipoprotein A-I and Surface Lipid Composition of Reconstituted Discoidal HDL on Cholesterol Efflux from Cultured Fibroblasts

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• 作者：Yuwei Zhao ; Daniel L. Sparks ; and Yves L. Marcel
• 刊名：Biochemistry
• 出版年：1996
• 出版时间：December 24, 1996
• 年：1996
• 卷：35
• 期：51
• 页码：16510 - 16518
• 全文大小：316K
• 年卷期：v.35,no.51(December 24, 1996)
• ISSN：1520-4995

文摘

Five series of reconstituted discoidal HDL (LpA-I) particles havebeen prepared, and theirconstituents, apolipoprotein A-I (apoA-I),1-palmitoyl-2-oleoylphosphatidylcholine (POPC),unesterifiedcholesterol (UC), phosphatidylinositol (PI), or sphingomyelin (SM),have been systematically varied toelucidate the relationship between HDL composition and cholesterolefflux from non-cholesterol-loadedhuman skin fibroblasts. The physical properties, such ashydrodynamic diameters, -helix contents, andsurface potentials, of these LpA-I have been measured and related tothe ability of the LpA-I to acceptcellular cholesterol. The results show that for LpA-I particlescontaining 2, 3, or 4 apoA-I per particle,Lp4A-I are the best acceptors of cellular cholesterol, followed byLp3A-I and then Lp2A-I particles.Discoidal Lp2A-I with variations in POPC content, from 121 to 266mol/particle, show no difference intheir abilities to promote cholesterol efflux. Similarly,inclusion of 7 and 15 mol of free cholesterol toLp2A-I also does not affect their ability to accept cellularcholesterol. However, increasing the contentof either PI or SM, up to 20 mol/particle, is associated withsignificantly increased abilities of the LpA-Ito promote cholesterol efflux. The efflux of cellular cholesterolto discoidal LpA-I particles is independentof specific changes in apoA-I conformation and charge, but appears tobe positively related to majorchanges in the size of the lipoprotein particle. The studysuggests that in contrast to interlipoproteincholesterol transfers, the efflux of cholesterol from culturedfibroblasts is less sensitive to factors thataffect the frequency of molecular collisions and more dependent on theability of an HDL particle toadsorb and retain cholesterol molecules. Since SM and PI appear tomodulate this adsorption/desorptionof cholesterol to HDL, variations in the concentration of these lipidswithin HDL would be expected toaffect plasma cholesterol homeostasis.