Elevation of plasma high-density lipoprotein concentration reduces interleukin-1-induced expression of E-selectin in an in vivo model of acute inflammation

Background-Although there is strong evidence that plasma HDL levers correla te inversely with the incidence of coronary artery disease, the precise mec hanism(s) for the protective effect of HDLs remains unclear. We recently sh owed that HDLs inhibit endothelial cell expression of cytokine induced leuk ocyte adhesion molecules in vitro. Our study therefore sought to test the h ypothesis that elevating the level of circulating HDLs would inhibit endoth elial cell activation in vivo. Methods and Results-We used a porcine model of inflammation previously esta blished in our laboratory, in which the level of vascular endothelial cell expression of E-selectin in interleukin (IL)-1 alpha -induced skin lesions was measured by the uptake of a radiolabeled anti-E-selectin antibody (1.2B 6). Porcine plasma HDL levels were elevated by use of a bolus injection of reconstituted discoidal HDL (recHDL). These particles resemble nascent HDL particles in shape and contain apolipoprotein A-I as the sole protein and s oybean phosphatidylcholine as the sole phospholipid. We found that recHDLs inhibited the expression of IL-1 alpha -induced E-selectin by porcine aorti c endothelial cells in vitro, confirming that the inhibitory effect is cons erved with synthetic HDLs and demonstrating that the phenomenon is not rest ricted to human endothelial cells. In vivo, elevating the circulating level of HDLs approximate to 2-fold led to significant inhibition of basal and I L-1 alpha -induced E-selectin expression by porcine microvascular endotheli al cells. Conclusions-These observations demonstrate the potential anti-inflammatory action of HDLs and provide support for the further investigation of the mec hanisms underlying the inhibitory effects of HDLs on endothelial cell activ ation.