Influence of apoA-I and apoE on the formation of serum amyloid A-containing lipoproteins in vivo and in vitro.
Serum amyloid A (SAA) circulates bound to HDL3 during the acute-phase response (APR), and recent evidence suggests that elevated levels of SAA may be a risk factor for cardiovascular disease. In this study, SAA-HDL was produced in vivo during the APR and without the APR by injection of an adenoviral vector expressing human SAA-1. SAA-HDL was also produced in vitro by incubating mouse HDL with recombinant mouse SAA and by SAA-expressing cultured hepatoma cells. Whether produced in vivo or in vitro, SAA-HDL floated at a density corresponding to that of human HDL3 (d 1.12 g/ml) separate from other apolipoproteins, including apolipoprotein A-I (apoA-I; d 1.10 g/ml) when either apoA-I or apolipoprotein E (apoE) was present. In the absence of both apoA-I and apoE, SAA was found in VLDL and LDL, with low levels in the HDL and the lipid-poor fractions suggesting that other HDL apolipoproteins are incapable of facilitating the formation of SAA-HDL. We conclude that SAA does not exist in plasma as a lipid-free protein. In the presence of HDL-associated apoA-I or apoE, SAA circulates as SAA-HDL with a density corresponding to that of human HDL3. In the absence of both apoA-I and apoE, SAA-HDL is not formed and SAA associates with any available lipoprotein.
Cabana
Veneracion G
VG
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Feng
Ning
N
Reardon
Catherine A
CA
Lukens
John
J
Webb
Nancy R
NR
de Beer
Frederick C
FC
Getz
Godfrey S
GS
D000210:Acute-Phase Reaction / Q000097:blood*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood*; D053440:Lipoproteins, HDL3; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D014161:Transduction, Genetic
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; C499308:Rag2 protein, mouse; D000685:Serum Amyloid A Protein; C064655:V(D)J recombination activating protein 2