Ability of reconstituted high density lipoproteins to inhibit cytokine-induced expression of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells

Previous studies have shown that both high density lipoproteins (HDL) isola ted from human plasma and reconstituted HDL (rHDL) are effective inhibitors of adhesion molecule expression in human endothelial cells. In this study rHDL have been used to investigate whether HDL particle shape, size, apolip oprotein composition or lipid composition are important determinants of the ability of HDL to inhibit the TNF-alpha induced expression of vascular cel l adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (H UVECs), On the basis of these studies it is possible to draw several firm c onclusions. i) Neither phospholipid-containing vesicles nor lipid-free apol ipoprotein (apo) A-I inhibit VCAM-1 expression in HUVECs. ii) Simple discoi dal complexes containing only phospholipid and apoA-I (discoidal (A-I)rHDL) are sufficient to inhibit the TNF-alpha-induced expression of VCAM-1 in HU VECs, iii) Spherical apoA-I-containing rHDL (spherical (A-I)rHDL) are super ior to discoidal (A-I)rHDL as inhibitors, iv) The particle size of spherica l (A-I)rHDL has no influence on the inhibition. v) Spherical rHDL that cont ain apoA-I are superior as inhibitors of VCAM-1 to those containing apoA-II when the rHDL preparations are equated for apolipoprotein molarity, Howeve r, when compared at equivalent particle molarities, this difference is no l onger apparent, vi) Replacement of cholesteryl esters with triglyceride in the core of spherical (A-I)rHDL has no effect on the ability of these parti cles to inhibit VCAM-1 expression. From these results it is tempting to spe culate that variations in inhibitory activity may contribute to the variati ons observed in the anti-atherogenicity of different HDL subpopulations.