Abstract 670: Serum Amyloid A May Attenuate the Loss of HDL Efflux Capacity During Human Endotoxemia
Background: Acute inflammation is associated with increased HDL serum amyloid A (HDL-SAA) coincident altered HDL function. Recent studies suggest that HDL-SAA may promote cholesterol efflux via SR-BI and ABCA1. However, it is uncertain whether SAA attenuates inflammation-induced loss of HDL efflux function in vivo and there are no studies of SAA and HDL efflux during human inflammation.
Methods: As part of a 60-hour human endotoxemia protocol [LPS 3 ng/kg LPS; n=20; 50% male, 80% Caucasian, mean age 27.3±4.8], we examined changes in HDL-SAA and lipids, ex-vivo HDL induced 3H-cholesterol efflux from FU5AH cells (SR-BI model) and cAMP stimulated J774s (ABCA1 model) and the relationship between HDL-SAA and efflux capacity. Spearman correlations and repeated measures analysis of variance and were applied to the data.
Results: The capacity of the HDL fraction to efflux 3H-cholesterol from FU5AH (18% reduction, p<0.001) and J774 (70% reduction, p<0.001) cells was reduced after LPS coinciding with marked reduction transiently in HDL phospholipids (22% reduction, P<0.01). Prior to LPS, efflux was related to HDL phospholipid and apoA-I levels but these correlations were lost following LPS. SAA levels in HDL were low prior to LPS and did not correlate with efflux. Following LPS, the absolute HDL-SAA level (2.20±2.41 @baseline vs 109.1±34.5 @12h and 187.7±74.6 ug/ml @24 h) and the HDL SAA/apoA-I ratio (0.032 @ baseline vs 1.70 @12h and 3.25 @24h) increased dramatically. At 12 hours, HDL-SAA did not correlate with HDL efflux capacity; however, by 24 hours, when HDL-SAA content was greatest and efflux was recovering, HDL-SAA levels were the single strongest lipid or apoprotein predictor of HDL efflux from the FU5AH SR-BI model (r2=0.421, p=0.022). The correlation between HDL-SAA and J774 ABCA1 efflux was not significant (r2=0.195, p=0.151 at 24 hours).
Conclusion: Human endotoxemia induces transient reduction in HDL efflux capacity. A gradual but marked enrichment in HDL-SAA following LPS may serve to limit the loss in HDL efflux capacity via the SR-BI pathway. Our studies provide in vivo support for a protective role for SAA in mitigating the negative impact of inflammation on HDL efflux function in human inflammation.