Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response: Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures

B. J. Van Lenten, S. Y. Hama, F. C. De Beer, D. M. Stafforini, T. M. McIntyre, S. M. Prescott, B. N. La Du, A. M. Fogelman, M. Navab

Research output: Contribution to journalArticlepeer-review

726 Scopus citations

Abstract

We previously reported that high density lipoprotein (HDL) protects against the oxidative modification of low density lipoprotein (LDL) induced by artery wall cells causing these cells to produce pro-inflammatory molecules. We also reported that enzyme systems associated with HDL were responsible for this anti-inflammatory property of HDL. We now report studies comparing HDL before and during an acute phase response (APR) in both humans and a croton oil rabbit model. In rabbits, from the onset of APR the protective effect of HDL progressively decreased and was completely lost by day three. As serum amyloid A (SAA) levels in acute phase HDL (AP-HDL) increased, apo A-I levels decreased 73%. Concomitantly, paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH) levels in HDL declined 71 and 90%, respectively, from days one to three. After day three, there was some recovery of the protective effect of HDL. AP-HDL from human patients and rabbits but not normal or control HDL (C-HDL) exhibited increases in ceruloplasmin (CP). This increase in CP was not seen in acute phase VLDL or LDL. C-HDL incubated with purified CP and re-isolated (CP-HDL), lost its ability to inhibit LDL oxidation. Northern blot analyses demonstrated enhanced expression of MCP-1 in coculture cells treated with AP-HDL and CP-HDL compared to C-HDL. Enrichment of human AP-HDL with purified PON or PAF-AH rendered AP-HDL protective against LDL modification. We conclude that under basal conditions HDL serves an anti-inflammatory role but during APR displacement and/or exchange of proteins associated with HDL results in a pro-inflammatory molecule.

Original languageEnglish
Pages (from-to)2758-2767
Number of pages10
JournalJournal of Clinical Investigation
Volume96
Issue number6
StatePublished - Dec 1995

Keywords

  • Apo A-I
  • Atherosclerosis
  • Ceruloplasmin
  • PAF acetylhydrolase
  • Paraoxonase
  • SAA

ASJC Scopus subject areas

  • General Medicine

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