Abstract
Several subspecies of human high density lipoprotein (HDL) have been shown to exist, and particle size is one parameter that can be used to distinguish them. Recently, a small HDL subspecies has been described that may be a particularly efficient acceptor of peripheral cell unesterified (free) cholesterol (FC). To address the effects of particle size on the ability of HDL to remove FC from cells, homogeneous, well defined HDL particles were reconstituted (rHDL) that varied in particle diameter within the size range of human HDL particles (7-13 nm). The abilities of each of these particles to remove cellular FC from mouse L-cells and rat Fu5AH hepatoma cells were compared on the basis of their phospholipid (PL) content as well as on a per particle basis. The effect of particle size was also examined using small unilamellar vesicles (SUV) of 25 nm in diameter and large unilamellar vesicles (LUVs) of 70-180 nm in diameter. The SUV were prepared by sonication, and the LUVs were prepared by extrusion techniques. The FC efflux efficiency of these particles (in order of decreasing efficiency) was: rHDL > SUV > LUV when compared on the basis of acceptor PL content across a range of concentrations (i.e. at a given PL concentration for these three acceptor classes, smaller particles were more efficient). The FC efflux differences between the rHDL and the vesicles were not due to the absence of apolipoprotein in the vesicles. No difference was detected among the rHDL of varying size, nor was a difference detected among the LUVs of varying size when compared on the basis of PL content. When the FC efflux data for rHDL and LUVs were normalized on the basis of the number of acceptor particles present at a given PL concentration, a correlation was found between acceptor particle radius and the ability to accept cellular FC with larger particles being the most efficient. However, the dependence of the rate of FC efflux on acceptor particle size was not quantitatively the same within the rHDL and LUV classes of acceptor particles. The dependence of FC efflux on acceptor particle size may reflect differing abilities of the variously sized acceptor particles to access the region very close to the cell plasma membrane where most of the FC removal is expected to occur.
Highlights
Several subspecies of human high density lipoprotein (HDL) have been shown to exist, and particle size is one parameter that can be used to distinguish them
When the FC efflux data for reconstituting well defined HDL particles (rHDL) and large unilamellar vesicles (LUVs) were normalized on the basis ofthe number of acceptor particles present at a given PL concentration, a correlation was found between acceptor particle radius and the ability to accept cellular FC with larger particles being the most efficient
The concept of high density lipoprotein (HDL)l heterogeneity has become a topic of great interest because of recent reports by several investigators that HDL subspecies may playa important role in the various stages of reverse cholesterol transport [1,2,3,4], the postulated process by which excess peripheral cell cholesterol is transported to the liver for catabolism [5]
Summary
Several subspecies of human high density lipoprotein (HDL) have been shown to exist, and particle size is one parameter that can be used to distinguish them. Of particular interest are the studies of Fielding et al [9, 10], which have demonstrated that a minor charge subspecies of human HDL may be a important factor in the first step of reverse cholesterol transport, the removal of cellular unesterified (free) cholesterol (FC) from cells. One characteristic of this particle is its small size (70 kDa) [9] with respect to the bulk of human plasma HDL (180-390 kDa) [11]. Such studies of HDL size subspecies have been hindered by the high degree of structural and compositional heterogeneity that is inherent in even highly purified preparations from human plasma
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