Raised levels of circulating endothelial cells in systemic sclerosis

OBJECTIVE: Circulating endothelial cells (CECs) have been described in different conditions with vascular injury. Vascular abnormalities play a key role in the pathogenesis of Systemic Sclerosis (SSc). The aim of our study was to look for the presence of CECs in SSc patients and to evaluate their clinical significance. METHODS: We studied 52 SSc patients and 40 healthy controls (HC). Five-parameter, 3-color flow cytometry was performed with a FACScan. CECs were defined as CD45 negative, CD31 and P1H12 positive, and activated CECs as CD45 negative and P1H12, CD62, or CD106 positive. RESULTS: Total and activated CEC counts were significantly higher in SSc patients when compared with HC and positively correlated with disease activity score. We found a significant association between CECs and disease activity; as regard with organ involvement, CEC number correlate with the severity of pulmonary hypertension. CONCLUSIONS: Raised counts of CECs may represent direct evidence of active vascular disease in SSc as regard as visceral involvement, the association between CECs and pulmonary hypertension suggest a relevant role for CECs as a marker of prominent endothelial involvement

Endothelial progenitor cells in systemic sclerosis: their possible role in angiogenesis

BACKGROUND: Recently, several studies have demonstrated the presence of circulating endothelial progenitors (CEPs) responsible for angiogenesis. Notably, these cells are able to migrate to ischemic tissues and differentiate in situ in mature endothelial cells. Aim of this study was to assess the presence of CEPs in the peripheral blood of patients with Sistemic Sclerosis (SSc) and evaluate their significance as an attempt of re-vascularization MATERIAL AND METHODS: Samples of peripheral blood from 40 healthy subjects and 56 patients with SSc were studied. Five-parameter, 3-color flow cytometry was performed with a FACScan. CEPs were defined as CD45 negative, CD34 and CD133 positive. In addition, plasma levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected by commercial ELISA (R&D Systems). RESULTS: Levels of CEPs (CD133+/CD34+/CD45-) were significantly higher in patients with SSc in comparison to HC (P = 0.01). No correlation was found between CEPs and any clinical parameter of disease neither activity score. CEPs were significantly higher in the group of patients with early disease, while their number decreased in the late phases of disease. Plasma levels of VEGF, but not bFGF, were significantly higher in SSc in comparison to HC (P<0.001) but no correlation was found between VEGF concentrations and CEP number. CONCLUSIONS: The presence of CEPs in patients with SSc suggest that sclerodermic hypoxic tissues could induce the mobilization of bone-marrow derived cells in an attempt to provided new vessels, in the early phase of the disease, at least

Circulating endothelial cells as a marker of ongoing vascular disease in systemic sclerosis

Objective Circulating endothelial cells (CECs) have been described in different conditions involving vascular injury. Vascular abnormalities play a key role in the pathogenesis of systemic sclerosis (SSc). The aim of this study was to search for the presence of CECs in patients with SSc and to evaluate their clinical associations and possible pathogenic role. Methods The study cohort included 46 patients with SSc and 40 healthy controls. Five-parameter, 3-color flow cytometry was performed with a FACScan. CECs were defined as CD45 negative, CD34 positive, and P1H12 positive, and activated CECs were defined as CD45 negative and P1H12 positive, CD62 positive, or CD106 positive. Progenitors were identified as CD34 positive and CD133 positive. Results Total and activated CEC counts were significantly higher in SSc patients compared with healthy controls and were positively correlated with the disease activity score. With respect to visceral involvement, significant correlation was observed between the CEC number and the severity of pulmonary hypertension. High levels of endothelial progenitors were observed in patients with SSc, and the counts were higher in the early stages of disease. Conclusion The presence of CECs in patients with SSc may represent direct evidence of endothelial disease and may be a promising new clinical marker for active SSc. Notably, the association between CECs and pulmonary hypertension and impaired carbon monoxide diffusing capacity was evident in patients with limited cutaneous SSc only, suggesting an important role for CECs in this disease subset with prominent vascular changes. Detection of circulating endothelial progenitors may represent a response to vascular ischemia in early SSc, as an attempt at revascularization

Bone marrow endothelial progenitors are defective in systemic sclerosis

Objective. Vascular abnormalities represent the main component of the pathobiol. of systemic sclerosis (SSc), progressing from structural derangements of the microcirculation with abortive neoangiogenesis to final vessel loss. Since circulating endothelial progenitor cells (EPCs) are important in the vascular repair process, we undertook this study to examine their nos. in the peripheral blood (PB) of SSc patients and to evaluate whether their status is related to impaired quant. and/or qual. aspects of the bone marrow (BM) microenvironment. Methods. Circulating EPCs from 62 SSc patients were evaluated by flow cytometry and characterized as CD45 neg. and CD133 pos. BM EPCs, identified as CD133 pos., were isolated from 14 SSc patients and grown to induce endothelial differentiation. In addn., progenitor nos. and functional properties of hematopoietic and stromal compartments were analyzed by various assays. Results. We found that EPCs were detectable in the PB of patients with SSc, and their no. was significantly increased in patients with early-stage disease but not in those with late-stage disease. All of the examd. BM samples contained reduced nos. of EPCs and stromal cells, both of which were functionally impaired. Both endothelial and stromal progenitors expressed vascular endothelial growth factor receptor, indicating that BM is strongly induced to differentiate into the endothelial lineage; furthermore, only BM EPCs from patients with early disease led to endothelial differentiation in vitro. Conclusion. This study provides the first demonstration that in SSc, there is a complex impairment in the BM microenvironment involving both the endothelial and mesenchymal stem cell compartments and that this impairment might play a role in defective vasculogenesis in scleroderma. [on SciFinder (R)

Anti-chromatin antibodies in juvenile rheumatoid arthritis

Objective: to evaluate the prevalence and clinical significance of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA). Methods: IgG anti-chromatin Abs were detected by an enzyme-linked immunosorbent assay (ELISA), in sera of 94 children with JRA (10 children with systemic, 38 with polyarticular and 46 with oligoarticular disease onset). As control group, 33 age- and-sex-matched healthy children (HC) were also examined. Results: Abs to chromatin were detected in 24/94 (25,5%) of children suffering from JRA. Particularly, the higher prevalence of anti-chromatin Abs has been found in children with oligoarticular (30,4%) and polyarticular (23,7%) onset JRA. In these groups Abs titers were significantly higher compared to systemic JRA and HC (p=0.003). Anti-chromatin Abs were observed more frequently in patients with oligoarticular disease and chronic uveitis (21,7%). Furthermore, higher levels of anti-chromatin Abs has been found in all the patients treated with anti-TNFα therapy (p<0.0001). Conclusions: our results confirm previous data about the prevalence of anti-chromatin Abs in JRA. These Abs were significantly higher in the group of patients with oligoarticular onset with past or present hystory of ocular involvement and in the group with polyarticular JRA treated with biologic therapy. A long-term follow-up study could be useful to evaluate the potential utility of these autoantibodies

Simvastatin reduces endothelial activation and damage but is partially ineffective in inducing endothelial repair in systemic sclerosis

OBJECTIVE: To investigate whether statins may improve endothelial function in systemic sclerosis (SSc) by evaluating the effects of simvastatin on vasculogenesis [indicated by the expansion of circulating endothelial progenitor cells (EPC)] and the markers of vascular injury in the peripheral blood of patients with SSc. METHODS: Twenty SSc patients with normal cholesterol concentrations and 20 hypercholesterolemic subjects were allocated to receive 20 mg/day simvastatin for 12 weeks. Peripheral blood samples were collected before and 12 weeks after initiation of treatment, and 4 weeks after discontinuation. Five-parameter, 3-color flow cytometry was performed with a FacScan to enumerate EPC and mature circulating endothelial cells (CEC). Levels of soluble E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, interleukin 6, and endothelin-1 were assessed by commercial ELISA. RESULTS: Simvastatin treatment significantly increased EPC in the hypercholesterolemic group, but failed to improve the EPC levels in the SSc patients, mainly in patients with late disease. Baseline levels of CEC were significantly higher in SSc patients compared with controls and at the end of the treatment they were significantly decreased. Regarding other markers of endothelial activation, we found that all the cytokine levels decreased in a statistically significant manner in the treated patients. CONCLUSION: Treatment with simvastatin results in rapid and significant improvement of measures of endothelial activation, suggesting a potential role of statins in the treatment of peripheral vascular disease in SSc. The lack of effect on increase of EPC confirms our previous findings of a defective endothelial stem cell recruitment in the bone marrow of SSc patients. This could indicate that the potential effectiveness of statins in SSc could mainly be ascribed to their effectiveness in modulating endothelial activation mechanism

Endothelial progenitor cells in systemic sclerosis: their possible role in angiogenesis

Background: Recently, several studies have demonstrated the presence of circulating endothelial progenitors (CEPs) responsable for angiogenesis. Notably, these cells are able to migrate to ischemic tissues and differentiate in situ in mature endothelial cells. Aim of this study was to assess the presence of CEPs in the peripheral blood of patients with Sistemic Sclerosis (SSc) and evaluate their significance as an attempt of re-vascularization Material and methods: Samples of peripheral blood from 40 healthy subjects and 56 patients with SSc were studied. Five-parameter, 3-color flow cytometry was performed with a FACScan. CEPs were defined as CD45 negative, CD34 and CD133 positive. In addition, plasma levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected by commercial ELISA (R&amp;D Systems). Results: Levels of CEPs (CD133+/CD34+/CD45-) were significantly higher in patients with SSc in comparison to HC (P = 0.01). No correlation was found between CEPs and any clinical parameter of disease neither activity score. CEPs were significantly higher in the group of patients with early disease, while their number decreased in the late phases of disease. Plasma levels of VEGF, but not bFGF, were significantly higher in SSc in comparison to HC (P<0.001) but no correlation was found between VEGF concentrations and CEP number. Conclusions: The presence of CEPs in patients with SSc suggest that sclerodermic hypoxic tissues could induce the mobilization of bone-marrow derived cells in an attempt to provided new vessels, in the early phase of the disease, at least