Lack of effect of serum amyloid A (SAA) on the ability of high-density lipoproteins to inhibit endothelial cell adhesion molecule expression

Studies have been conducted to determine whether the ability of high densit y lipoproteins (HDL) to inhibit the cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells is altered by the p resence in HDL of the acute phase reactant, serum amyloid-A (SAA). Preparat ions of HDL3 were isolated on two separate occasions from the plasma of eac h of 19 patients: the first was collected before and the second 3 days afte r undergoing coronary artery bypass graft surgery. Whereas the preoperative HDL3 sample contained no SAA, in the postoperative sample SAA accounted fo r an average of 42% of the HDL3 protein. The preoperative HDL3 and postoper ative, SAA-enriched HDL3 were identical in terms of their ability to inhibi t the tumour necrosis factor-alpha (TNF-alpha)-induced expression of VCAM-1 in human umbilical vein endothelial cells (HUVECs). To assess the effect o f having an even greater SAA enrichment of HDL3, samples of HDL3 were incub ated with purified SAA, which displaced almost all of the apoAI and about 4 0% of the apoAII from the HDL3. This in vitro SAA-enriched HDL3 inhibited t he TNF-alpha -induced expression of VCAM-1 in HUVECs in a concentration dep endent manner, which was identical to that of the unmodified HDL3. The pres ence of SAA did not alter the cell-surface binding of HDL3 to endothelial c ells. It has been concluded that the presence of SAA in HDL has no effect o n the ability of these lipoproteins either to inhibit the expression of VCA M-1 in endothelial cells or to bind to proteins on the endothelial cell sur face. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.