Abstract 388: Impact of Individual Acute Phase Serum Amyloid A Isoforms on HDL Metabolism in Mice

Abstract

The acute phase reactant serum amyloid A (SAA) is an HDL apolipoprotein that exhibits biological activities as a pro-inflammatory mediator, but its physiological function(s) are poorly understood. Possible functional differences between SAA1.1 and SAA2.1, the two major SAA isoforms, are also unclear. Mice deficient in either SAA1.1 or SAA2.1 were used to investigate SAA isoform plasma clearance rates and effects on HDL structure, composition and apolipoprotein catabolism. The absence of either isoform did not affect the size of the normally enlarged HDL found in acute phase wild type mice, and did not result in significant changes in HDL lipid composition. Plasma clearance rates of normal and acute phase HDL apolipoproteins were determined using native HDL particles. The fractional clearance rates (FCR’s) of apoA-I, apoA-II and SAA were distinct, indicating that neither normal nor acute phase particles are cleared as intact particles. No significant difference was found between the FCR’s of SAA1.1 and SAA2.1 in acute phase mice, suggesting that the selective deposition of SAA1.1 observed in amyloid plaques is not associated with a difference in the rates of plasma clearance of the isoforms. In the absence of the HDL receptor SR-BI, the clearance rate of SAA was reduced by about 30% and remained significantly greater compared to that of apoA-I and apoA-II, indicating a relatively minor role of SR-BI in SAA clearance. These studies contribute to our understanding of the metabolism of SAA and its effects on acute phase HDL composition and catabolism.