Speciation of Human Plasma High-Density Lipoprotein (HDL): HDL Stability and Apolipoprotein A-I Partitioning

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• 作者：Henry J. Pownall ; Brian D. Hosken ; Baiba K. Gillard ; Catherine L. Higgins ; Hu Yu Lin ; John B. Massey
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：June 26, 2007
• 年：2007
• 卷：46
• 期：25
• 页码：7449 - 7459
• 全文大小：495K
• 年卷期：v.46,no.25(June 26, 2007)
• ISSN：1520-4995

文摘

The distribution of apolipoprotein (apo) A-I between human high-density lipoproteins (HDL)and water is an important component of reverse cholesterol transport and the atheroprotective effects ofHDL. Chaotropic perturbation (CP) with guanidinium chloride (Gdm-Cl) reveals HDL instability byinducing the unfolding and transfer of apo A-I but not apo A-II into the aqueous phase while forminglarger apo A-I deficient HDL-like particles and small amounts of cholesteryl ester-rich microemulsions(CERMs). Our kinetic and hydrodynamic studies of the CP of HDL species separated according to sizeand density show that (1) CP mediated an increase in HDL size, which involves quasi-fusion of surfaceand core lipids, and release of lipid-free apo A-I (these processes correlate linearly), (2) >94% of theHDL lipids remain with an apo A-I deficient particle, (3) apo A-II remains associated with a very stableHDL-like particle even at high levels of Gdm-Cl, and (4) apo A-I unfolding and transfer from HDL towater vary among HDL subfractions with the larger and more buoyant species exhibiting greater stability.Our data indicate that apo A-I's on small HDL (HDL-S) are highly dynamic and, relative to apo A-I onthe larger more mature HDL, partition more readily into the aqueous phase, where they initiate the formationof new HDL species. Our data suggest that the greater instability of HDL-S generates free apo A-I andan apo A-I deficient HDL-S that readily fuses with the more stable HDL-L. Thus, the presence of HDL-Ldrives the CP remodeling of HDL to an equilibrium with even larger HDL-L and more lipid-free apo A-Ithan with either HDL-L or HDL-S alone. Moreover, according to dilution studies of HDL in 3 M Gdm-Cl, CP of HDL fits a model of apo A-I partitioning between HDL phospholipids and water that is controlledby the principal of opposing forces. These findings suggest that the size and relative amount of HDLlipid determine the HDL stability and the fraction of apo A-I that partitions into the aqueous phase whereit is destined for interaction with ABCA1 transporters, thereby initiating reverse cholesterol transport or,alternatively, renal clearance.