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

Autor: Nicole Domingo, Françoise Chanussot, Henri Portugal, Sandra Grès, Catherine Farnarier, Vincent Saunier, Emmanuelle Arlotto, Valérie Marin, Elise Lombard, Anne-Marie Lorec, Denis Lairon
Rok vydání: 2005
Předmět:
Zdroj: Pathobiology. 72:213-219
ISSN: 1423-0291
1015-2008
DOI: 10.1159/000086791
Popis: 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.
Databáze: OpenAIRE