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Thromb Res. 2014 Mar;133(3):426-32. doi: 10.1016/j.thromres.2013.12.030. Epub 2013 Dec 30.

The proinflammatory effect of C-reactive protein on human endothelial cells depends on the FcγRIIa genotype.

Author information

1
Department of Cardiology and Angiology, University Hospital Erlangen, Erlangen, Germany. Electronic address: Dorette.Raaz@uk-erlangen.de.
2
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
3
Department of Cardiology and Angiology, University Hospital Erlangen, Erlangen, Germany.
4
Department of Rheumatology and Immunology, University Hospital Erlangen, Erlangen, Germany.

Abstract

INTRODUCTION:

The stimulatory effects of CRP (C-reactive protein) on endothelial cells are mainly mediated via FcγRIIa. This receptor exists in two different allotypes bearing either arginine (R131) or histidine (H131) at the extracellular amino acid position 131 of the mature protein, but only FcγRIIa-R131 displays high avidity for CRP. This study investigated the role of the FcγRIIa genotype in CRP-stimulated endothelial cells.

MATERIALS AND METHODS:

We tested the effects of CRP on expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin, as well as the endothelial release of pro-inflammatory molecules as a function of the FcγRIIa-genotype (FcγRIIa-H/H131, FcγRIIa-H/R131, FcγRIIa-R/R131) in HUVEC (Human Umbilical Vein Endothelial Cells). HUVEC were grouped according to their FcγRIIa status by genotyping with an allele specific nested-PCR. The expression of ICAM-1, VCAM-1, and E-selectin on HUVEC was detected by flow cytometry. The release of soluble markers (sCD40L, IL-6, IL-8, MCP-1, tPA, sP-selectin, and sVCAM-1) was measured using a multiplex assay for flow cytometry.

RESULTS AND CONCLUSIONS:

CRP-stimulated expression of ICAM-1 and E-selectin was dependent on the specific FcγRIIa-genotype, with most pronounced induction in HUVEC with the FcγRIIa-R/R genotype, followed by H/R and H/H. In accordance with this finding, the supernatants of stimulated HUVEC with the R/R genotype showed significantly higher levels of tPA, MCP-1, and IL-6. Our data show that CRP stimulates the expression of adhesion molecules and the release of soluble markers by HUVEC as a function of the FcγRIIa-genotype. These findings could be relevant in the context of risk stratification in patients with cardiovascular disease.

KEYWORDS:

C-reactive protein; Cell adhesion molecules; Coronary artery disease; Cytokines; Fcγ receptor IIa gene polymorphisms

PMID:
24440139
DOI:
10.1016/j.thromres.2013.12.030
[Indexed for MEDLINE]

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