title: Impact of individual acute phase serum amyloid A isoforms on HDL metabolism in mice.
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.
authors.affiliation: Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Physiology, University of Kentucky Medical Center, Lexington, KY 40536 Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536.
authors.forename: Maria C
authors.initials: MC
authors.lastname: de Beer
authors.affiliation: Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536 Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Wroblewski
authors.affiliation: Departments of Statistics and Biostatistics, University of Kentucky, Lexington, KY 40506.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Charnigo
authors.affiliation: Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536 Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536.
authors.forename: Ailing
authors.initials: A
authors.lastname: Ji
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536 Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, KY 40536.
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Webb
authors.affiliation: Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536 Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536.
authors.forename: Frederick C
authors.initials: FC
authors.lastname: de Beer
authors.affiliation: 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.
authors.forename: Deneys R
authors.initials: DR
authors.lastname: van der Westhuyzen
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000737:chemistry; D016633:Apolipoprotein A-II / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000737:chemistry; D051379:Mice; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics*; D051122:Scavenger Receptors, Class B / Q000097:blood / Q000737:chemistry; D000685:Serum Amyloid A Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D020033:Protein Isoforms; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D000685:Serum Amyloid A Protein
keywords: acute phase protein; apolipoproteins; high density lipoprotein; inflammation; lipoproteins/metabolism; scavenger receptor class B type 1; scavenger receptors