Anionic Peptide Factor/Phosphatidylcholine Particles Promote the Inhibition of Vascular Cell Adhesion Molecule-1 in Human Umbilical Vein Endothelial Cells

Abstract

Objective: High-density lipoproteins (HDLs) have significant cardiovascular benefits by retarding the progression of atherosclerosis. One of the mechanisms is the inhibition by HDLs of the vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells. Our objective was to test the effect on VCAM-1 expression by the human umbilical vein endothelial cells (HUVEC) of a minor HDL₂ and HDL₃ apolipoprotein, the anionic peptide factor (APF). The peptide has previously been found to develop some beneficial effects against atherosclerosis, i.e. by promoting the cholesterol efflux from endothelial cells. Methods: We examined the effects of two HDL apolipoproteins A-I and APF, either in presence or absence of phosphatidylcholines (PCs), or free PCs, on the expression of VCAM-1 by HUVEC. The cells were stimulated with either the tumor necrosis factor-α (TNFα, 500 pg/ml) or the calcium bound to heparin (10 µg Ca²⁺/ml, 50 µg heparin/ml). Results: In the presence of TNFα, only the free PCs (0.25 and 1 mM) developed an inhibitory effect (up to 50%). In the absence of TNFα and in the presence of calcium bound to heparin, either the lipid-free APF (3.5 µM) or the APF/PC complexes (1:57 molar ratio) or the free PCs (0.25 mM) exhibited a substantial inhibitory effect (72, 71 and 42%, respectively). Conclusion: Our present findings suggest for the first time that one of the mechanisms of the antiatherogenic action of APF involves the inhibition of VCAM-1 expression by HUVEC. The peptide, through its phospholipid-binding and its calcium antagonist abilities, appears to confer on the HDLs a protective effect against the early cellular event of the inflammatory process.