C-reactive protein inhibits cholesterol efflux from human macrophage-derived foam cells

Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):519-26. doi: 10.1161/ATVBAHA.107.159467. Epub 2007 Dec 20.


Objective: The objective of this study was to determine the effects and potential mechanisms of C-reactive protein (CRP) on cholesterol efflux from human macrophage foam cells, which may play a critical role in atherogenesis.

Methods and results: Human THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) were preincubated with acetylated LDL and [3H]-cholesterol to form foam cells, which were then treated with apolipoprotein A-I (apoA-I) or HDL for cholesterol efflux assay. Clinically relevant concentrations of CRP significantly reduced cholesterol efflux from THP-1 and PBMCs to apoA-I or HDL. CRP significantly decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) and ABCG1, whereas it increased superoxide anion production. Furthermore, CRP substantially activated ERK1/2 in THP-1-derived foam-like cells. Reducing superoxide anion by antioxidant seleno-L-methionine or SOD mimetic (MnTBAP) effectively abolished the CRP-induced decrease in cholesterol efflux and the expression of ABCA1 and ABCG1. Inhibiting ERK1/2 activation by its specific inhibitor PD98059 or by a dominant negative mutant of ERK2 could also block CRPs action on THP-1 cells.

Conclusions: CRP inhibits cholesterol efflux from human foam cells derived from THP-1 and PBMCs in vitro though oxidative stress, ERK1/2 activation, and downregulation of intracellular cholesterol transport molecules ABCA1 and ABCG1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Analysis of Variance
  • Antioxidants / pharmacology
  • Atherosclerosis / physiopathology
  • Biological Transport
  • Blotting, Western
  • C-Reactive Protein / metabolism*
  • Cells, Cultured
  • Cholesterol Esters / metabolism*
  • Foam Cells / drug effects
  • Foam Cells / metabolism*
  • Humans
  • Macrophages / cytology
  • Probability
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Superoxides / metabolism


  • ATP-Binding Cassette Transporters
  • Antioxidants
  • Cholesterol Esters
  • Superoxides
  • C-Reactive Protein