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J Lipid Res. 2016 Jun;57(6):969-79. doi: 10.1194/jlr.M062174. Epub 2016 Mar 27.

Impact of individual acute phase serum amyloid A isoforms on HDL metabolism in mice.

Author information

1
Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536.
2
Physiology, University of Kentucky Medical Center, Lexington, KY 40536 Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536.
3
Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536 Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536.
4
Departments of Statistics and Biostatistics, University of Kentucky, Lexington, KY 40506.
5
Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536 Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, KY 40536.
6
Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536 Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536 Molecular and Cellular Biochemistry, University of Kentucky Medical Center, Lexington, KY 40536 dvwest1@uky.edu.

Abstract

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.

KEYWORDS:

acute phase protein; apolipoproteins; high density lipoprotein; inflammation; lipoproteins/metabolism; scavenger receptor class B type 1; scavenger receptors

PMID:
27018443
PMCID:
PMC4878182
DOI:
10.1194/jlr.M062174
[Indexed for MEDLINE]
Free PMC Article

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