Influence of apoA-I and apoE on the formation of serum amyloid A-containing lipoproteins in vivo and in vitro

J Lipid Res. 2004 Feb;45(2):317-25. doi: 10.1194/jlr.M300414-JLR200. Epub 2003 Nov 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute-Phase Reaction / blood*
  • Adenoviridae / genetics
  • Animals
  • Apolipoprotein A-I / genetics
  • Apolipoprotein A-I / metabolism*
  • Apolipoproteins E / metabolism*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • Lipoproteins, HDL / blood*
  • Lipoproteins, HDL3
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Serum Amyloid A Protein / metabolism*
  • Transduction, Genetic


  • Apolipoprotein A-I
  • Apolipoproteins E
  • DNA-Binding Proteins
  • Lipoproteins, HDL
  • Lipoproteins, HDL3
  • Rag2 protein, mouse
  • Serum Amyloid A Protein
  • V(D)J recombination activating protein 2