INHIBITION OF VCAM-1 EXPRESSION IN ENDOTHELIAL-CELLS BY RECONSTITUTEDHIGH-DENSITY-LIPOPROTEINS

Plasma-derived high density lipoproteins (HDL) were found to inhibit c ytokine-induced expression of endothelial cell adhesion molecules. Her e we used apolipoprotein-specific reconstituted HDL (rHDL) made with p hosphatidylcholine (PC) and three different apolipoproteins to identif y the HDL components involved in this effect. rHDL containing apolipop rotein A-I (apoA-I), the disulfide-linked form of the apoA-I-Milano va riant, 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 c oncentration dependent in the range of 0.1-1.0 mg/ml (protein). PC lip osomes slightly depressed TNF alpha-induced VCAM-1 expression (16% vs 43-50% for the various rHDL), whereas the lipid-free apolipoproteins h ad no effect. The protein component of HDL is involved in the inhibiti on of VCAM-1 expression in HUVEC through a rather unspecific mechanism , as three apolipoproteins with remarkably different primary structure display very similar activity. (C) 1997 Academic Press.