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

ABSTRACT

Studies have been conducted to determine whether the ability of high density lipoproteins (HDL) to inhibit the cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells is altered by the presence in HDL of the acute phase reactant, serum amyloid-A (SAA). Preparations of HDL(3) were isolated on two separate occasions from the plasma of each of 19 patients the first was collected before and the second 3 days after undergoing coronary artery bypass graft surgery. Whereas the preoperative HDL(3) sample contained no SAA, in the postoperative sample SAA accounted for an average of 42% of the HDL(3) protein. The preoperative HDL(3) and postoperative, SAA-enriched HDL(3) were identical in terms of their ability to inhibit the tumour necrosis factor-alpha (TNF-alpha)-induced expression of VCAM-1 in human umbilical vein endothelial cells (HUVECs). To assess the effect of having an even greater SAA enrichment of HDL(3), samples of HDL(3) were incubated with purified SAA, which displaced almost all of the apoAI and about 40% of the apoAII from the HDL(3). This in vitro SAA-enriched HDL(3) inhibited the TNF-alpha-induced expression of VCAM-1 in HUVECs in a concentration dependent manner, which was identical to that of the unmodified HDL(3). The presence of SAA did not alter the cell-surface binding of HDL(3) to endothelial cells. It has been concluded that the presence of SAA in HDL has no effect on the ability of these lipoproteins either to inhibit the expression of VCAM-1 in endothelial cells or to bind to proteins on the endothelial cell surface.