SERUM AMYLOID-A (SAA) - INFLUENCE ON HDL-MEDIATED CELLULAR CHOLESTEROL EFFLUX

Normal high density lipoprotein (N-HDL) is remodeled during acute phas e (AP) reactions by the association of serum amyloid A (SAA) and the d epletion of apolipoprotein (ape) A-I. To determine the impact of this remodeling on HDL function, the capacities of N-HDL and AP-HDL to asso ciate with and promote cholesterol efflux from human monocytic THP-1 c ells were compared. THP-1 cells preferentially bound AP-HDL compared w ith N-HDL. Examination of the AP-HDL particles bound to THP-1 cells re vealed a disproportionate association of an apoSAA-enriched, apoA-I-de pleted subpopulation compared with the composition of the starting mat erial: However, N-HDL and AP-HDL promoted cholesterol efflux from THP- I cells equally efficiently and in a dose-dependent manner. When N-HDL was experimentally remodeled with apoSAA to achieve an apoprotein com position similar to that of the preferentially bound particles, cellul ar cholesterol efflux was reduced by 30%. The remodelling of HDL with apoSAA during the acute phase reaction alters cholesterol efflux only when apoSAA constitutes more than 50% of the HDL protein.