Eloisa Romano

Azienda Ospedaliero Universitaria Careggi, Firenzuola, Tuscany, Italy

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Publications (28)112.33 Total impact

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    ABSTRACT: Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and hyperplasia. Tumor necrosis factor-α (TNF-α) plays a pivotal role in RA by interfering with the Fas-Fas ligand (FasL) proapoptotic pathway. We investigated the circulating levels of soluble Fas (sFas) and soluble FasL (sFasL), and their possible correlation with disease activity and improvement after anti-TNF-α treatment in RA.
    The Journal of rheumatology. 09/2014;
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    ABSTRACT: Haemophilic arthropathy (HA) is characterized by chronic proliferative synovitis leading to cartilage destruction and shares some pathological features with rheumatoid arthritis (RA). Apoptosis has been implicated in RA pathogenesis, and an agonistic anti-Fas monoclonal antibody (mAb) was found to induce RA fibroblast-like synoviocyte (FLS) apoptosis and suppress synovial hyperplasia in animal models of RA. The aim of this study was to evaluate the effect of anti-Fas mAb on HA-FLS. FLS were isolated from knee synovial biopsies from six HA patients, six RA patients and six healthy subjects. The expression of Fas in synovial biopsies was investigated by immunohistochemistry. FLS were stimulated with anti-Fas mAb at different concentrations, alone or in combination with tumour necrosis factor-α (TNF-α) and basic fibroblast growth factor (bFGF). Fas expression in FLS was assessed by Western blot. Cell viability was studied with the WST-1 assay. Active caspase-3 levels were measured using ELISA and Western blot. A strong Fas-immunoreactivity was observed in different cells of HA synovium, including FLS, inflammatory cells and endothelial cells. Fas antigen was constitutively overexpressed in cultured HA-FLS. Anti-Fas mAb had a significant cytotoxicity on HA-FLS in a dose-dependent manner, either alone or in combination with TNF-α and bFGF. These cytotoxic effects were due to the ability of anti-Fas to induce HA-FLS apoptosis, as shown by the increased active caspase-3 levels. Anti-Fas mAb exhibited a more pronounced pro-apoptotic effect on HA-FLS than RA-FLS. Fas antigen is highly expressed on HA-FLS and its stimulation by anti-Fas mAb may be an effective strategy to induce HA-FLS apoptosis.
    Haemophilia 11/2013; · 3.17 Impact Factor
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    ABSTRACT: Microvascular damage and defective angiogenesis and vasculogenesis have a major role in the pathogenesis of systemic sclerosis (SSc). Epidermal growth factor-like domain 7 (EGFL7) is a proangiogenic molecule which is predominantly expressed and secreted by endothelial cells and their progenitors and controls vascular development and integrity. In this study, we investigated the possible involvement of EGFL7 in SSc. Serum EGFL7 levels from 60 patients with SSc and 35 age- and sex-matched healthy controls were examined by colorimetric sandwich enzyme-linked immunosorbent assay. The expression of EGFL7 in forearm skin biopsies (n = 16 SSc, n = 10 controls), cultured dermal microvascular endothelial cells (MVECs) (n = 3 SSc, n = 3 controls) and late-outgrowth peripheral blood endothelial progenitor cell (EPC)-derived endothelial cells (n = 15 SSc, n = 8 controls) was investigated by immunofluorescence and Western blotting. Serum EGFL7 levels were detectable in 68.6% of healthy controls and 45% of SSc cases (P < 0.05). Circulating levels of EGFL7 were significantly decreased in SSc patients compared with healthy controls (P = 0.01). Serum levels of EGFL7 were significantly lower in both limited cutaneous SSc and diffuse cutaneous SSc patients than in controls (P = 0.02 and P = 0.04, respectively). In SSc, decreased serum EGFL7 levels were significantly correlated with the severity of nailfold capillary abnormalities. Patients with the most severe capillary changes and digital ulcers had serum EGFL7 levels significantly lower than healthy controls, while the EGFL7 levels did not differ significantly between controls and SSc patients with less capillary damage and lack of digital ulcers. Endothelial EGFL7 expression was strongly downregulated or even almost completely undetectable in SSc-affected dermis compared with controls (P < 0.001). In cultured SSc dermal MVECs and late-outgrowth peripheral blood EPC-derived endothelial cells, EGFL7 was significantly downregulated compared with cells obtained from healthy subjects (P < 0.01 and P < 0.001, respectively). Our findings suggest that the loss of EGFL7 expression in endothelial cells and their progenitors might play a role in the development and progression of peripheral microvascular damage and the defective vascular repair process characteristic of SSc.
    Arthritis research & therapy 10/2013; 15(5):R165. · 4.27 Impact Factor
  • Annals of the rheumatic diseases 04/2013; · 8.11 Impact Factor
  • Annals of the rheumatic diseases 02/2013; · 8.11 Impact Factor
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    Arthritis and Rheumatism. 09/2012; 35(1):247-257.
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    ABSTRACT: Hemarthrosis triggers hemophilic arthropathy, involving the target joints. The histopathogenesis of blood-induced joint damage remains unclear. The triad of receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG; RANK-RANKL-OPG) controls bone turnover. Our aim was to evaluate RANK-RANKL-OPG expression in the synovium of hemophilic patients with severe arthropathy. Synovial biopsies were obtained from 18 patients with hemophilic arthropathy and 16 with osteoarthritis (OA) who were undergoing total knee replacement and synovectomy. The severity of hemophilic arthropathy was evaluated according to ultrasonography score, the World Federation of Hemophilia (WFH) orthopedic joint scale, and the radiographic Pettersson score. RANK-RANKL-OPG expression was examined by immunohistochemistry and Western blotting. Serum levels of soluble RANKL (sRANKL) and OPG from an extended group of 67 patients with hemophilic arthropathy and 30 healthy controls were measured by ELISA. The mean ultrasonography, WFH orthopedic joint scale, and Pettersson scores in patients with hemophilic arthropathy indicated severe arthropathy. A decreased expression of OPG was found in hemophilic arthropathy synovium compared with patients with OA. RANK and RANKL immunopositivity was strong in the lining and sublining layers in hemophilic arthropathy synovial tissue. Western blotting confirmed the immunohistological findings. Serum levels of sRANKL and OPG in patients with hemophilia were lower than in healthy controls. In hemophilic arthropathy, the synovium highly expressed RANK and RANKL, whereas OPG immunopositivity decreased, suggesting an osteoclastic activation. Low tissue expression of OPG paralleled the serum levels of this protein and the severity of hemophilic arthropathy assessed by ultrasonography, Pettersson, and WFH orthopedic joint scale scores.
    The Journal of Rheumatology 07/2012; 39(8):1678-86. · 3.26 Impact Factor
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    ABSTRACT: Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of CAV1 gene single nucleotide polymorphisms (SNP) with SSc. A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning the CAV1-CAV2 gene locus were obtained from a genome-wide scan conducted in a French population (564 SSc patients, 1776 controls). Three CAV1 SNP (rs926198, rs959173, rs9920) displaying the most significant associations with SSc and/or clinical phenotypes were then genotyped in an Italian population (791 SSc patients, 843 controls). CAV1 protein expression in skin biopsies was investigated by immunohistochemistry and western blotting. In the French population, the CAV1 rs959173 C minor allele showed a significant protective association with susceptibility to SSc (OR 0.71, 95% CI 0.59 to 0.86, p(adjusted)=0.009), and with the subset of patients with limited cutaneous SSc (OR 0.71, 95% CI 0.56 to 0.89, p(adjusted)=0.018). The association was replicated in the Italian population and strengthened in the combined populations through Cochran-Mantel-Haenszel meta-analysis (SSc: pooled OR 0.81, 95% CI 0.71 to 0.92, p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95% CI 0.69 to 0.93, p=0.0053). Genotype/protein expression correlations revealed that the rs959173 C protective allele was associated with increased CAV1 protein expression. These results add CAV1 to the list of SSc susceptibility genes and provide further evidence for the contribution of this pathway in the fibrotic process that characterises SSc pathogenesis.
    Annals of the rheumatic diseases 03/2012; 71(6):1034-41. · 8.11 Impact Factor
  • Arthritis Research & Therapy 02/2012; 14(1). · 4.30 Impact Factor
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    ABSTRACT: To determine serum concentrations and tissue expression of matrix metalloproteinase-12 (MMP-12) and their correlation with clinical features in patients with systemic sclerosis (SSc). Serum MMP-12 levels from 72 patients with SSc and 42 healthy volunteers were examined by ELISA. Immunohistochemical expression of MMP-12 was analysed in skin biopsies from 20 patients with SSc and 13 healthy subjects and lung biopsies from three patients with SSc-related interstitial lung disease (ILD) and five controls. Circulating levels of MMP-12 were significantly increased in patients with SSc compared with healthy controls. Serum MMP-12 levels were significantly higher in both patients with limited cutaneous SSc and those with diffuse cutaneous SSc than in healthy controls, and correlated positively with the extent of skin involvement. MMP-12 levels were raised in SSc patients with ILD compared with patients without ILD, and correlated with severity of lung restriction. Increased serum levels of MMP-12 were also associated with the presence of digital ulcers and severity of nailfold capillary abnormalities. In contrast to almost undetectable MMP-12 expression in healthy skin, MMP-12 was strongly expressed in keratinocytes, dermal endothelial cells, fibroblasts/myofibroblasts and inflammatory cells in the skin of patients with SSc. Affected lung tissue from patients with SSc-related ILD showed strong MMP-12 expression in capillary vessels, inflammatory cells, alveolar macrophages and fibroblasts in the thickened alveolar septa, while faint expression was observed in normal lung tissue. MMP-12 levels are increased in patients with SSc and are associated with severity of skin and pulmonary fibrosis and peripheral vascular damage.
    Annals of the rheumatic diseases 01/2012; 71(6):1064-72. · 8.11 Impact Factor
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    ABSTRACT: To characterise bone marrow-derived mesenchymal stem cells (MSCs) from patients with systemic sclerosis (SSc) for the expression of factors implicated in MSC recruitment at sites of injury, angiogenesis and fibrosis. The study also analysed whether the production/release of bioactive mediators by MSCs were affected by stimulation with cytokines found upregulated in SSc serum and tissues, and whether MSCs could modulate dermal microvascular endothelial cell (MVEC) angiogenesis. MSCs obtained from five patients with early severe diffuse SSc (SSc-MSCs) and five healthy donors (H-MSCs) were stimulated with vascular endothelial growth factor (VEGF), transforming growth factor β (TGFβ) or stromal cell-derived factor-1 (SDF-1). Transcript and protein levels of SDF-1 and its receptor CXCR4, VEGF, TGFβ(1) and receptors TβRI and TβRII were evaluated by quantitative real-time PCR, western blotting and confocal microscopy. VEGF, SDF-1 and TGFβ(1) secretion in culture supernatant was measured by ELISA. MVEC capillary morphogenesis was performed on Matrigel with the addition of MSC-conditioned medium. In SSc-MSCs the basal expression of proangiogenic SDF-1/CXCR4 and VEGF was significantly increased compared with H-MSCs. SSc-MSCs constitutively released higher levels of SDF-1 and VEGF. SDF-1/CXCR4 were upregulated after VEGF stimulation and CXCR4 redistributed from the cytoplasm to the cell surface. VEGF was increased by SDF-1 challenge. VEGF, TGFβ and SDF-1 stimulation upregulated TGFβ(1), TβRI and TβRII in SSc-MSCs. TβRII redistributed from the cytoplasm to focal adhesion contacts. SSc-MSC-conditioned medium showed a greater proangiogenic effect on MVECs than H-MSCs. Experiments with blocking antibodies showed that MSC-derived cytokines were responsible for this potent proangiogenic effect. SSc-MSCs constitutively overexpress and release bioactive mediators/proangiogenic factors and potentiate dermal MVEC angiogenesis.
    Annals of the rheumatic diseases 08/2011; 70(11):2011-21. · 8.11 Impact Factor
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    ABSTRACT: Systemic sclerosis (SSc) is characterized by widespread microangiopathy, fibrosis, and autoimmunity. Despite the lack of angiogenesis, the expression of vascular endothelial growth factor A (VEGF) was shown to be upregulated in SSc skin and circulation; however, previous studies did not distinguish between proangiogenic VEGF(165) and antiangiogenic VEGF(165)b isoforms, which are generated by alternative splicing in the terminal exon of VEGF pre-RNA. We investigated whether VEGF isoform expression could be altered in skin and circulation of patients with SSc. Here, we show that the endogenous antiangiogenic VEGF(165)b splice variant is selectively overexpressed at both the mRNA and protein levels in SSc skin. Elevated VEGF(165)b expression correlated with increased expression of profibrotic transforming growth factor-β1 and serine/arginine protein 55 splicing factor in keratinocytes, fibroblasts, endothelial cells, and perivascular inflammatory cells. Circulating levels of VEGF(165)b were significantly higher in patients with SSc than in control subjects. Microvascular endothelial cells (MVECs) isolated from SSc skin expressed and released higher levels of VEGF(165)b than healthy MVECs. Transforming growth factor-β1 upregulated the expression of VEGF(165)b and serine/arginine protein 55 in both SSc and healthy MVECs. In SSc MVECs, VEGF receptor-2 was overexpressed, but its phosphorylation was impaired. Recombinant VEGF(165)b and SSc-MVEC-conditioned medium inhibited VEGF(165)-mediated VEGF receptor-2 phosphorylation and capillary morphogenesis in healthy MVECs. The addition of anti-VEGF(165)b blocking antibodies abrogated the antiangiogenic effect of SSc-MVEC-conditioned medium. Capillary morphogenesis was severely impaired in SSc MVECs and could be ameliorated by treatment with recombinant VEGF(165) and anti-VEGF(165)b blocking antibodies. In SSc, a switch from proangiogenic to antiangiogenic VEGF isoforms may have a crucial role in the insufficient angiogenic response to chronic ischemia.
    Circulation Research 06/2011; 109(3):e14-26. · 11.86 Impact Factor
  • Annals of the rheumatic diseases 05/2011; 70(10):1876-8. · 8.11 Impact Factor
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    ABSTRACT: Light transmission aggregation (LTA) is considered the reference method to identify residual platelet reactivity (RPR) in high-risk patients with coronary artery disease on clopidogrel treatment. An international standardization of this technique is still ongoing and different concentrations of adenosine diphosphate (ADP) as the agonist for LTA have been used to evaluate the inhibitory effect of clopidogrel treatment. To evaluate RPR, LTA was performed using different ADP concentrations (2, 5, 10, and 20 μmol/L) in 466 high-risk patients with coronary artery disease on dual antiplatelet therapy who underwent percutaneous coronary intervention and in 46 healthy subjects. A VerifyNow P2Y12 assay was assessed as a point-of care system. Imprecision studies showed higher coefficients of variation for LTA by 2 and 5 μmol/L ADP (healthy subjects: 4.7% and 3.9%; patients: 6.8% and 5.2%, respectively) in comparison with those obtained determining LTA using 10 and 20 μmol/L ADP (healthy subjects: 2.2% and 2.3%; patients: 2.7% and 3.1%, respectively). In patients, a significant difference (P < 0.0001) between mean values of LTA obtained with all ADP concentrations was found, even if LTA data were significantly correlated (at least: rho = 0.88, P < 0.0001). However, data from 10 and 20 μmol/L ADP LTA were very similar and highly concordant (k = 95.9%). All agreements were significant (for all P < 0.0001), in particular the agreement between 10 and 20 μmol/L ADP LTA was very good (k = 0.86, P < 0.0001). A moderate agreement between VerifyNow and both 10 and 20 μmol/L ADP LTA was observed. LTA by 10 and 20 μmol/L ADP gave equivalent percentages of aggregation and highly concordant results in terms of RPR in patients with coronary artery disease on clopidogrel. Significant concordant results were observed between both 10 and 20 μM ADP LTA and VerifyNow. This suggests that a concentration of 10 μmol/L ADP may be considered adequate for the identification of RPR of patients on clopidogrel and should be preferred for standardization LTA.
    Therapeutic drug monitoring 02/2011; 33(1):94-8. · 2.43 Impact Factor
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    ABSTRACT: Microparticles (MPs) are increased in diseases characterised by endothelial injury. Kawasaki disease (KD) damages the endothelium provoking life-threatening involvement of coronary arteries. To compare KD MPs vs. controls. METHODS. Thirty KD and 20 controls were enrolled. MPs were stained with monoclonal antibodies against platelets, endothelial cells (EC), monocytes, T and B cells, neutrophils, and quantified by FACS. The total number of MPs was significantly increased in KD versus controls (193x105±0.6x105 vs. 94x105±0.9x105 million/ml plasma p=0.01) and vs. KD after IVIG therapy (132x105±0.4x105million/ml plasma p=0.01). EC and T cells were the major source of MPs in KD (72x105±1x105 vs. 3x105±0.9x105million/ml plasma for T cells p=0.005; 76x105±0.7x105 vs. 45x105±0.4x105 million/ml plasma for EC p<0.02) followed by MPs derived from platelets (13x105±0.3x105 vs. 3x105±0.9x105 million/ml plasma p=0.028). Cell-derived MPs B were 17x105±0.4x105 vs. 20x105±0.8x105million/ml plasma in controls (p=0.7). No significant differences were observed in KD MPs derived from monocytes and neutrophils. After IVIG administration, a significant decrease of MPs derived from platelets (3x105±0.2x105 million/ml plasma p=0.03), EC (9x105±0.4x105 million/ml plasma p=0.01), T cells (72x105±1x105 million/ml plasma p=0.02) and B cells (7x105±0.3x105 million/ml plasma p=0.02) was observed. The number of KD MPs is significantly increased and EC and T cells are the major source. MPs may develop from endothelial damage and cell activation. Their role as markers of disease activity or as contributors to endothelial derangement in KD has to be further investigated.
    Clinical and experimental rheumatology 02/2011; 29(1 Suppl 64):S121-5. · 2.66 Impact Factor
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    ABSTRACT: Background and objectiveRheumatoid arthritis (RA) is a chronic systemic autoimmune disease, in which neovascularisation of the synovium is regarded as a crucial step in its development and progression. Lymphatic neovascularisation has been observed in RA joints. Junctional adhesion molecule A (JAM-A) and JAM-C regulate leucocyte-endothelial cell (EC) interactions. JAMs also interact at inter-EC junctions regulating vascular permeability and are implicated in pathophysiological processes involving leukocyte transmigration, tight junction assembly and angiogenesis.The aim of this study was to investigate the role of JAM-A and JAM-C in mediating the lymphoangiogenic process in RA synovium.Materials and methodsSynovial biopsies from RA and osteoarthritic (OA) patients, used as control, has been collected during arthroplasty or synovectomy. Synovial sections were stained with primary antibodies (Abs) antihuman JAM-A or JAM-C followed by fluorochrome-conjugated secondary Abs. The lymphatic EC specific marker podoplanin (D2-40) was used to differentiate blood (D2-40−) and lymphatic (D2-40+) vessels.ResultsImmunohistochemical analysis showed, in RA synovium, the presence of abundant D2-40+ structures, identifiable as lymphatic vessels. Many D2-40+ cells were also found in the intimal lyning layer, specially in the hyperplasic areas. Lymphatic vessels were distributed in the sublining, specially around blood vessels. Clusters of D2-40+ cells were also found in the inflammatory infiltrate, in structures resembling new lymphatic vessels. In all sections from RA, JAM-A and JAM-C were observed on almost all vasculature including the lymphatic (D2-40+) and blood vessels (D2-40−). Initial lymphatic vessels reacted with anti-JAM-A and anti-JAM-C. In the synovial lining, JAM-A and JAM-C were expressed on D2-40+ macrophage-like synoviocites. D2-40+ cells in the inflammatory infiltrate showed positivity for both JAM-A and JAM-C. The immunostaining for both JAMs was weaker in OA than in RA synovium.Conclusion This results confirm the presence of an increased number of lymphatic vessels in RA synovial tissue. Moreover, the authors observed D2-40+ structures, mostly around pre-existing blood vessels, indicating the development of a new lymphatic network in the synovial sublining. The presence of D2-40+ cells in the inflammatory infiltrate and in the macrophage-like synoviocites, lead us to hypothesise that in RA, macrophages are activated and may function as lymphatic precursors. In RA synovium, both JAM-A and JAM-C are expressed in all D2-40+ cells, indicating their participation in the inflammatory process and intercellular junction assembly. Their expression in new lymphatic vessels and in D2-40+ cells stimulated to form new vessels, confirm their involvement in the lymphoangiogenic process occurring in RA.
    Annals of The Rheumatic Diseases - ANN RHEUM DIS. 01/2011; 70(2).
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    ABSTRACT: Systemic sclerosis (SSc) is a complex systemic disease characterised by fibrosis of the skin and internal organs, vasculopathy, and activation of the immune system. The complex pathophysiology of SSc implies the potential involvement of 'culprit' genes, either individually or, more likely, together, in driving the disease process. Most of the studies that have provided evidence for the contribution of various genes/loci in SSc pathogenesis are based on a candidate gene approach, on the basis of a shared autoimmune genetic background with other autoimmune diseases, such as systemic lupus erythematosus. In fact, autoimmune genes seem to play a pivotal role in SSc pathogenesis, while less is known about the genetic involvement in vasculopathy and fibrosis. Recently, the availability of genome-wide association studies, which make it possible to screen single-nucleotide polymorphisms across the entire genome without previous knowledge of candidate regions or genes, has yielded a wealth of new genetic susceptibility loci leading to the identification of new pathogenetic mechanisms of complex genetic disorders. In this article, we aim to provide a comprehensive review of recent studies on the genetics of SSc, including genes associated with autoimmunity, fibrosis, and vascular disease. We also discuss the most relevant data obtained in genetic association studies of large populations that included a replication strategy, or studies for which independent replication was available.
    Clinical and experimental rheumatology 01/2011; 29(2 Suppl 65):S75-86. · 2.66 Impact Factor
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    ABSTRACT: Objective Junctional adhesion molecule (JAM)-A and JAM-C regulate leucocyte-endothelial cell (EC) interactions. JAMs also interact at inter-EC junctions regulating vascular permeability and are implicated in pathophysiological processes involving leucocyte transmigration, tight junction assembly and angiogenesis. SSc is characterised by early perivascular inflammatory infiltrates, EC damage and defective angiogenesis. We investigated the expression of JAMs in SSc skin and dermal microvascular ECs (MVECs) challenged with SSc sera.Methods Skin biopsies were obtained from the involved skin of 16 SSc patients (10 early, 6 late phase) and from 10 controls. Skin sections were stained with primary antibodies (Abs) anti-human JAM-A or JAM-C followed by fluorochrome-conjugated secondary Abs. The lymphatic EC specific marker podoplanin (D2-40) was used to differentiate blood (D2-40–) and lymphatic (D2-40+) vessels. Human dermal MVECs were stimulated with VEGF or early SSc (n=5) and control (n=4) sera for 1, 6, 24 h. MVECs were double-immunolabeled for JAM-C and the human tight junction protein zonula occludens-1 (ZO-1), or for JAM-A and the pro-angiogenic αVβ3 integrin. Immunostained tissue sections and cells were examined by confocal laser scanning microscopy. Densitometric analysis of staining intensity was performed using ImageJ software.ResultsIn control skin, constitutive expression of JAM-A was observed in blood and lymphatic ECs, fibroblasts and keratinocytes. In early SSc skin, JAM-A expression was increased in blood and lymphatic vessels and fibroblasts. Moreover, perivascular inflammatory cells showed strong JAM-A positivity. In late SSc, JAM-A expression was weaker than in controls. JAM-C was weakly expressed in controls. In early SSc, JAM-C expression was markedly observed in blood and lymphatic ECs, fibroblasts, and inflammatory cells. Instead, in late SSc JAM-C expression was similar to controls. Stimulation of MVECs with early SSc sera increased the cell surface expression of JAM-A and αVβ3 integrin. JAM-C expression was found in MVEC cytoplasm at basal conditions and under stimulation with control sera. Upon early SSc sera challenging, JAM-C was rapidly recruited to tight junctions where it colocalised with ZO-1, with the maximun effect after 1 h. Similar effects were observed after 1 h VEGF stimulation.ConclusionsJAMs are differentially expressed in early and late SSc skin. Early SSc sera affect the expression and subcellular localisation of JAMs in dermal MVECs. In SSc, JAMs may participate in early inflammatory process, EC activation and impaired angiogenesis.
    Annals of The Rheumatic Diseases - ANN RHEUM DIS. 01/2011; 70(2).
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    ABSTRACT: Systemic sclerosis (SSc) is a connective tissue disorder characterized by microvascular and fibrotic changes in the skin and internal organs. The role of blood vessel dysfunction in the pathogenesis of SSc has been extensively investigated, but few studies have addressed the involvement of the lymphatic vascular system. Our aim was to evaluate dermal lymphatic vessels in patients with SSc according to different phases of skin involvement. Skin biopsies were obtained from the forearm of 25 SSc patients (10 early/15 late-stage disease) and 13 healthy controls. Skin sections were immunostained for podoplanin (D2-40), which is selectively expressed in lymphatic endothelial cells, and examined by confocal laser scanning microscopy. Lymphatic vessels were counted in the papillary and reticular dermis. Data were analyzed using Student's t test. The number of lymphatic vessels was significantly reduced in the papillary and reticular dermis of SSc patients compared with controls. In early SSc, lymphatic vessel counts were not different from controls in the papillary dermis, and showed a trend toward a reduction in the reticular dermis. In late SSc, a significant reduction in lymphatic vessels compared with controls was found in both the papillary and reticular dermis. The number of lymphatic vessels in the papillary dermis of late SSc was significantly lower than in early SSc. In SSc, lymphatic microangiopathy is linked to the progression of skin involvement. The progressive disappearance of lymphatic vessels may have a critical pathogenetic role in the progression of SSc from an early edematous phase to overt fibrosis.
    The Journal of Rheumatology 11/2010; 38(2):297-301. · 3.26 Impact Factor
  • Annals of The Rheumatic Diseases - ANN RHEUM DIS. 01/2010; 69(2).