Anionic peptide factor/phosphatidylcholine particles promote the inhibition of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells.
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-alpha (TNFalpha, 500 pg/ml) or the calcium bound to heparin (10 microg Ca2+/ml, 50 microg heparin/ml).


RESULTS
In the presence of TNFalpha, only the free PCs (0.25 and 1 mM) developed an inhibitory effect (up to 50%). In the absence of TNFalpha and in the presence of calcium bound to heparin, either the lipid-free APF (3.5 microM) 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).


CONCLUSIONS
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.
Lombard
Elise
E
UMR 476 INSERM/1260 INRA, Faculté de Médecine, Marseille, France.
Marin
Valérie
V
Domingo
Nicole
N
Grès
Sandra
S
Lorec
Anne-Marie
AM
Saunier
Vincent
V
Arlotto
Emmanuelle
E
Portugal
Henri
H
Lairon
Denis
D
Farnarier
Catherine
C
Chanussot
Françoise
F
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D010455:Peptides / Q000378:metabolism; D010713:Phosphatidylcholines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D010455:Peptides; D010713:Phosphatidylcholines; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D006493:Heparin