Published online before print January 10, 2005, doi: 10.1161/01.CIR.0000151875.21836.AE
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(Circulation. 2005;111:204-211.)
© 2005 American Heart Association, Inc.
Molecular Cardiology |
Depletion of Endothelial Progenitor Cells in the Peripheral Blood of Patients With Rheumatoid Arthritis
From the Division of Rheumatology (J.G., D.A., C.W.S., T.K., G.S., J.S.S.), Department of Internal Medicine III; the Division of Angiology (S.S., D.S.), Department of Internal Medicine II; and the Departments of Cardiothoracic Surgery (G.W.) and of Medical and Chemical Laboratory Diagnostics (I.S.), Medical University of Vienna; the Ludwig Boltzmann Institute of Experimental Endocrinology (W.W.) and Rheumatology (G.S., J.S.S.) and the Center of Molecular Medicine (G.S., J.S.S.) of the Austrian Academy of Sciences, Vienna, Austria.
Correspondence to Johannes Grisar, MD, Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail johannes.grisar{at}meduniwien.ac.at
Received April 29, 2004; revision received October 15, 2004; accepted October 15, 2004.
Background— Rheumatoid arthritis (RA) is characterized by increased cardiovascular morbidity and mortality that cannot be explained solely by traditional cardiovascular risk factors. Cardiovascular morbidity is related to disease activity and can be normalized by effective therapy. Because the quantity of endothelial progenitor cells (EPCs) in the peripheral blood is correlated inversely with cardiovascular risk, we studied whether such abnormalities could also be observed in patients with RA.
Methods and Results— EPCs were determined in 52 RA patients and in 16 healthy referents (HRs) by fluorescence-activated cell-sorting (FACS) analysis. Patients were divided into groups characterized by active disease (n=36) and low disease activity (n=16). Cells that were positive by flow cytometry for CD34/KDR/AC133 within the lymphocyte population were characterized as EPCs. Furthermore, in subgroups of patients, circulating EPCs were also quantified by a colony-forming unit (CFU) and a circulating angiogenic cell (CAC) assay. EPCs were significantly decreased in RA patients suffering from active disease compared with those from HRs, as measured by FACS analysis (0.026±0.002% versus 0.045±0.008%, respectively, P<0.05), CFU assay (mean of 5±2 versus 18±5 CFU/well in HRs, P<0.05), and CAC assay (mean of 7±2 versus 52±16 positive cells/high-power field, P<0.005). In contrast, the frequency of circulating EPCs from patients with low disease activity was comparable to that of healthy individuals (0.052±0.006% by FACS analysis), CFU assay (10±5 CFU/well), and CAC assay (mean of 25±5 positive cells). Moreover, EPC quantities in peripheral blood were correlated inversely with disease activity as assessed by the disease activity score (r=–0.38, P<0.01).
Conclusions— Our observations indicate that active RA is associated with a depletion of circulating EPCs. This might be one of several factors contributing to the increased cardiovascular risk in RA.
Key Words: progenitor cells • rheumatoid arthritis • angiogenesis • cardiovascular diseases • antibodies
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