The acute phase (AP) reactant serum amyloid A (SAA), an HDL apolipoprotein, exhibits pro-inflammatory activities, but its physiological function(s) are poorly understood. Functional differences between SAA1.1 and SAA2.1, the two major SAA isoforms, are unclear. Mice deficient in either isoform were used to investigate plasma isoform effects on HDL structure, composition, and apolipoprotein catabolism. Lack of either isoform did not affect the size of HDL, normally enlarged in the AP, and did not significantly change HDL composition. Plasma clearance rates of HDL apolipoproteins were determined using native HDL particles. The fractional clearance rates (FCRs) of apoA-I, apoA-II, and SAA were distinct, indicating that HDL is not cleared as intact particles. The FCRs of SAA1.1 and SAA2.1 in AP mice were similar, suggesting that the selective deposition of SAA1.1 in amyloid plaques is not associated with a difference in the rates of plasma clearance of the isoforms. Although the clearance rate of SAA was reduced in the absence of the HDL receptor, scavenger receptor class B type I (SR-BI), it remained significantly faster compared with that of apoA-I and apoA-II, indicating a relatively minor role of SR-BI in SAA’s rapid clearance. These studies enhance our understanding of SAA metabolism and SAA’s effects on AP-HDL composition and catabolism.

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Notes/Citation Information

Published in Journal of Lipid Research, v. 57, 6, p. 969-979.

This research was originally published in the Journal of Lipid Research. Kim, M., de Beer, M., Wroblewski, J., Charnigo, R., Ji, A., Webb, N., de Beer, F., and van der Westhuyzen, D. Journal of Lipid Research, 2016; 57:969-979. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

The copyright holder has granted the permission for posting the article here.

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Funding Information

This work was supported by National Institutes of Health Grant PO1HL086670 (to D.R.vdW.), National Institute of General Medical Sciences Grant 8 P20 GM103527, and VA CSR&D Merit Review Award (1l01CX000773) to N.R.W.

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The online version of this article (available at http://www.jlr.org) contains a supplement.

jlr.M062174-1.pdf (328 kB)
Supplemental figure IA-IB

jlr.M062174-2.pdf (58 kB)
Supplemental figure II

jlr.M062174-3.pdf (190 kB)
Supplemental figure IIIA-IIIB

jlr.M062174-4.pdf (125 kB)
Supplemental Table I: Primer sequences