Inhibition of VCAM-1 expression in endothelial cells by reconstituted high density lipoproteins.
Plasma-derived high density lipoproteins (HDL) were found to inhibit cytokine-induced expression of endothelial cell adhesion molecules. Here we used apolipoprotein-specific reconstituted HDL (rHDL) made with phosphatidylcholine (PC) and three different apolipoproteins to identify the HDL components involved in this effect. rHDL containing apolipoprotein A-I (apoA-I), the disulfide-linked form of the apoA-IMilano variant, or apoA-II, were all effective in inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 in TNF alpha- or LPS-stimulated HUVEC. The inhibition was concentration dependent in the range of 0.1-1.0 mg/ml (protein). PC liposomes slightly depressed TNF alpha-induced VCAM-1 expression (16% vs 43-50% for the various rHDL), whereas the lipid-free apolipoproteins had no effect. The protein component of HDL is involved in the inhibition of VCAM-1 expression in HUVEC through a rather unspecific mechanism, as three apolipoproteins with remarkably different primary structure display very similar activity.
Calabresi
L
L
Center E. Grossi Paoletti, Institute of Pharmacological Sciences, Milan, Italy.
Franceschini
G
G
Sirtori
C R
CR
De Palma
A
A
Saresella
M
M
Ferrante
P
P
Taramelli
D
D
D016632:Apolipoprotein A-I / Q000378:metabolism / Q000494:pharmacology; D016633:Apolipoprotein A-II / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects*
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1