ABSTRACT
OBJECTIVE: To compare levels of a range of endothelial progenitor cells (EPCs) and endothelial colony-forming units (CFUs) in control participants and RA patients, in addition to verifying whether levels of EPCs or CFUs are associated with clinical characteristics in RA patients. METHODS: Peripheral blood mononuclear cells (PBMCs) from 36 RA patients and 30 control participants were analysed by flow cytometry for EPCs defined by the expression of CD34/CD133, CD34/CD117, CD34/CD31, CD34/KDR and CD34/CD133/KDR. Endothelial cell colonies derived from culture of PBMCs were also assessed by CFU assay. RESULTS: No differences in levels of EPCs were observed in RA patients compared with controls. However, levels of EPCs were negatively associated with prognostic markers of poor disease status, but not cardiovascular (CV)-related risk factors. Furthermore, the majority of EPCs examined were negatively correlated with levels of RF. In contrast, CFU number was significantly reduced in RA patients compared with controls and was negatively associated with CV risk factors only. CONCLUSION: These findings indicate that more informative than comparing changes in absolute levels of EPCs, the examination of their relationship with clinical characteristics of RA patients can reveal significant associations, which may provide important clinical insights.
Subject(s)
Arthritis, Rheumatoid/blood , Hematopoietic Stem Cells/pathology , Aged , Blood Sedimentation , Cardiovascular Diseases/etiology , Cells, Cultured , Colony-Forming Units Assay , Endothelial Cells/pathology , Endothelium, Vascular/pathology , Female , Humans , Lymphocyte Count , Male , Prognosis , Rheumatoid Factor/blood , Risk Factors , Severity of Illness IndexABSTRACT
AIMS/HYPOTHESIS: In patients with type 2 diabetes, reduced levels of circulating endothelial progenitor cells have been reported and these have been correlated with disease severity. In this study, we examined a panel of markers widely used to identify progenitor and/or stem cells, and determined their association with disease severity in diabetic patients. Since expression of chemokine (C-X-C motif) receptor 4 (CXCR4) has been associated with mobilisation and recruitment of progenitor cells, CXCR4 expression was also analysed. METHODS: Peripheral blood mononuclear cells (PBMCs) from 98 patients with type 2 diabetes and 39 control individuals were analysed by flow cytometry for surface marker expression. RESULTS: Cells expressing different combinations of progenitor and/or stem cell markers were severely reduced in PBMCs of diabetic patients compared with those of control participants. Moreover, a number of these putative progenitor cell populations were negatively associated with disease severity. Reduced expression of CXCR4 and CD34/CXCR4-positive cells was also observed in diabetic patients. PBMCs expressing CXCR4 positively correlated with levels of progenitor cells in control participants but not in diabetic patients. Levels of putative progenitor and CXCR4-positive cells were further decreased in patients with diabetic complications, including cardiovascular and microvascular diseases. CONCLUSIONS/INTERPRETATION: A generalised decrease in a range of progenitor cell populations was observed in type 2 diabetic patients. This reduction was also negatively associated with disease severity.
Subject(s)
Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/pathology , Endothelial Cells/cytology , Hematopoietic Stem Cells/cytology , Receptors, CXCR4/metabolism , AC133 Antigen , Antigens, CD/metabolism , Antigens, CD34/metabolism , Biomarkers/metabolism , Diabetic Angiopathies/immunology , Diabetic Angiopathies/pathology , Female , Flow Cytometry , Glycoproteins/metabolism , Hematopoietic Stem Cells/metabolism , Humans , Male , Middle Aged , Peptides/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Receptors, CXCR4/immunology , Severity of Illness Index , Vascular Endothelial Growth Factor Receptor-2/metabolismABSTRACT
OBJECTIVES: Recent studies demonstrated in vivo the effectiveness of statins in reducing the inflammatory response in rheumatic diseases, and still more recently, simvastatin has been reported to inhibit in vitro IL-6 and IL-8 production by unstimulated fibroblast-like-synoviocytes (FLS) from rheumatoid arthritis (RA) patients. However, no data are available on the effect of statins on the production of these cytokines induced by IL-1, which plays a crucial role in joint inflammation in the course of active RA in vivo. METHODS: In 12 RA patients, synovial tissue specimens were taken to obtain cultures of FLS. Cultures were incubated with IL-1 +/- simvastatin (5-50 micromol/l), and IL-6 and IL-8 production was evaluated (ELISA), also following the addition of mevalonate and its isoprenoid derivatives. Moreover, nuclear factor-kB (NF-kB) activation (immunocytochemistry and Western Blot analysis) were also evaluated. RESULTS: Culture incubation with IL-1 produced a dramatic increase (up to 40-fold) in cytokine production with respect to unstimulated cells. Simvastatin significantly inhibited (about 20%) IL-6 and IL-8 production from IL-1-stimulated FLS. This effect was completely reverted by the concomitant incubation with mevalonate or geranylgeraniol (but not farnesol or squalene). Moreover, simvastatin produced a clear-cut inhibition of IL-1-induced NF-kB activation. CONCLUSION: Simvastatin significantly inhibits the production of IL-6 and IL-8 also in IL-1-stimulated FLS, even though to a lesser extent than in unstimulated cells, via a HMG-CoA-reductase block with an interference in prenylation process and NF-kB activation. Our results further support the rationale for the use of statins in the treatment of rheumatoid synovitis.
