Expression of serum amyloid A protein in the absence of the acute phase response does not reduce HDL cholesterol or apoA-I levels in human apoA-I transgenic mice

Hiroshi Hosoai, Nancy R. Webb, Jane M. Glick, Uwe J.F. Tietge, Matthew S. Purdom, Frederick C. De Beer, Daniel J. Rader

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Plasma concentrations of high density lipoprotein (HI)L) cholesterol and its major apolipoprotein (apo)A-I are significantly decreased in inflammatory states. Plasma levels of the serum amyloid A (SAA) protein increase markedly during the acute phase response and are elevated in many chronic inflammatory states. Because SAA is associated with HDL and has been shown to be capable of displacing apoA-I from HDL in vitro, it is believed that expression of SAA is the primary cause of the reduced HDL cholesterol and apoA-I in inflammatory states. In order to directly test this hypothesis, we constructed recombinant adenoviruses expressing the murine SAA and human SAA1 genes (the major acute phase SAA proteins in both species). These recombinant adenoviruses were injected intravenously into wild-type and human apoA-I transgenic mice and the effects of SAA expression on HDL cholesterol and apoA-I were compared with mice injected with a control adenovirus. Plasma levels of SAA were comparable to those seen in the acute phase response in mice and humans. However, despite high plasma levels of murine or human SAA, no significant changes in HDL cholesterol or apoA-I levels were observed. SAA was found associated with HDL but did not specifically alter the cholesterol or human apoA-I distribution among lipoproteins. In summary, high plasma levels of SAA in the absence of a generalized acute phase response did not result in reduction of HDL cholesterol or apoA-I in mice, suggesting that there are components of the acute phase response other than SAA expression that may directly influence HDL metabolism.

Original languageEnglish
Pages (from-to)648-653
Number of pages6
JournalJournal of Lipid Research
Volume40
Issue number4
StatePublished - Apr 1999

Keywords

  • Acute phase response
  • Adenoviral gene transfer
  • Apolipoprotein A-I
  • HDL metabolism
  • Serum amyloid A

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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