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Clin Exp Rheumatol. 2013 Mar-Apr;31(2):225-33. Epub 2012 Dec 13.

Certolizumab pegol attenuates the pro-inflammatory state in endothelial cells in a manner that is atheroprotective.

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1
University of Manchester, UK. sarahheathfield@hotmail.com

Abstract

OBJECTIVES:

Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and premature cardiovascular death. Anti-TNF therapy is thought to reduce clinical cardiovascular disease risk and improve vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to explore the effects of certolizumab pegol (CZP) on TNF-activated human aortic endothelial cells (HAoECs).

METHODS:

HAoECs were cultured in vitro and exposed to i) TNF alone, ii) TNF plus CZP, or iii) neither agent. Microarray analysis and quantitative polymerase chain reaction were used to analyse gene expression. Activation of NF-κB was investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was performed to detect microparticle release from HAoECs.

RESULTS:

TNF alone had strong effects on endothelial gene expression, while TNF and CZP together produced a global gene expression pattern similar to untreated controls. In particular, genes for E-selectin, VCAM-1 and ICAM-1 were significantly up-regulated by TNF treatment. Notably, the TNF/CZP cocktail prevented the up-regulation of these genes. TNF-induced nuclear translocation of NF-κB was abolished by treatment with CZP. In addition the increased production of endothelial microparticles in TNF-activated HAoECs was prevented by treatment with CZP.

CONCLUSIONS:

We have found at cellular level, that a clinically available TNF inhibitor, CZP i) reduces adhesion molecule expression; ii) prevents TNF-induced activation of the NF-κB pathway and iii) prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions.

PMID:
23295110
[Indexed for MEDLINE]

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