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


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.
Wang
Xinwen
X
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Liao
Dan
D
Bharadwaj
Uddalak
U
Li
Min
M
Yao
Qizhi
Q
Chen
Changyi
C
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000704:Analysis of Variance; D000975:Antioxidants / Q000494:pharmacology; D050197:Atherosclerosis / Q000503:physiopathology; D001692:Biological Transport; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000378:metabolism*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology; D011336:Probability; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013481:Superoxides / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D000975:Antioxidants; D002788:Cholesterol Esters; D013481:Superoxides; D002097:C-Reactive Protein