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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:519.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

C-Reactive Protein Inhibits Cholesterol Efflux From Human Macrophage-Derived Foam Cells

Xinwen Wang; Dan Liao; Uddalak Bharadwaj; Min Li; Qizhi Yao; Changyi Chen

From the Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy (X.W., D.L., U.B., M.L., Q.Y., C.C.), Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex; and the Department of Vascular Surgery (X.W.), 1st Teaching Hospital, China Medical University, Shenyang, China.

Correspondence to Changyi (Johnny) Chen, MD, PhD, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Mail stop: NAB-2010, Houston, TX 77030. E-mail jchen{at}bcm.tmc.edu

Abstract

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. Futhermore, 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.

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. 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 ABCA-1 and ABCG-1.

Key Words: C-reactive protein • macrophage • cholesterol efflux • ATP-binding membrane cassette transporter • superoxide anion • antioxidant

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