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Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells

K Herbrig^1,*, S Haensel^2,*, U Oelschlaegel³, F Pistrosch¹, S Foerster¹, J Passauer¹

¹ Nephrology, Department of Internal Medicine III, Technical University of Dresden, Dresden, Germany
² Rheumatology, Department of Internal Medicine III, Technical University of Dresden, Dresden, Germany
³ Haematology, Department of Internal Medicine I, Technical University of Dresden, Dresden, Germany

Correspondence to:
Dr K Herbrig
Department of Medicine III, Nephrology, Technical University of Dresden, Fetscherstrasse 74, 01309 Dresden, Germany; kayherbrig{at}web.de and haensel.s{at}debitel.net

Background: Rheumatoid arthritis (RA) is associated with increased morbidity and mortality attributable to accelerated atherosclerosis and cardiovascular events.

Objective: To determine the role played by endothelial progenitor cells (EPC) in the defence system against arteriosclerosis.

Methods: The number and function of EPC in 13 young patients with RA with low disease activity (DAS28 3.5 (0.3)) and 13 healthy control subjects was studied. Endothelial function was investigated by agonist-induced, endothelium dependent vasodilatation measured by the forearm blood flow technique. Migratory activity and adhesion of EPC to tumour necrosis factor (TNF) activated mature endothelial cells and components of the extracellular matrix were tested in vitro. Putative precursor populations (CD34⁺, CD34⁺/CD133⁺, and CD34⁺/KDR⁺ haematopoietic stem cells) were measured by flow cytometric analysis.

Results: Acetylcholine-induced, endothelium dependent vasodilatation was reduced by about 50% in patients with RA, indicating endothelial dysfunction, whereas endothelium-independent vasodilatation in response to glyceryl trinitrate was at control level. Significantly reduced numbers of EPC were found in the patients compared with controls. Migratory activity of EPC was decreased in patients with RA. Adhesion to mature endothelial cells after activation with TNF was enhanced only in controls. The adhesion to matrix proteins and the number of putative precursor cell lineages was comparable in both groups.

Conclusion: Endothelial dysfunction in patients with RA with low grade inflammation is associated with a reduced number and partial dysfunction of EPC. Further studies are needed to explore whether interventions that potentially ameliorate the number and function of EPC also improve endothelial function in these patients.

Abbreviations: Ach, acetylcholine; ANOVA, analysis of variance; DAS28, 28 joint count Disease Activity Score; DiLDL, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine labelled acetylated low density lipoprotein; EBM, endothelial basal medium; EFI, endothelial function index; EPC, endothelial progenitor cells; FBF, forearm blood flow; GTN, glyceryl trinitrate; HCAEC, human coronary artery endothelial cells; HPF, high power field(s); hsCRP, high sensitivity C reactive protein; IL, interleukin; MNCs, mononuclear cells; MTX, methotrexate; PBS, phosphate buffered saline; PI, propidium iodide; RA, rheumatoid arthritis; TNF, tumour necrosis factor ; VEGF, vascular endothelial growth factor

Keywords: rheumatoid arthritis; endothelial progenitor cells; endothelial dysfunction; forearm blood flow

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