Circulating chromogranin A reveals extra-articular involvement in patients with rheumatoid arthritis and curbs TNF-α-elicited endothelial activation (original) (raw)
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Journal of Leukocyte Biology, 2008
TNF-␣ plays an important role in the natural history of rheumatoid arthritis (RA), a systemic disease characterized by endothelial activation and synovial involvement with bone erosions. Neuroendocrine signals contribute as well to RA, but their role is poorly understood. We measured in 104 RA patients and in an equal number of sexand age-matched, healthy controls the blood levels of chromogranin A (CgA), a candidate marker linking the neuroendocrine system to TNF-␣-mediated vascular inflammation. CgA levels were significantly higher in patients with RA and remained stable over time. High levels of CgA were significantly associated with severe extra-articular manifestations, namely pulmonary fibrosis, rheumatoid vasculitis, serositis, and peripheral neuropathy. RA sera curbed the response of human microvascular endothelial cells to TNF-␣, as assessed by the expression ICAM-1, the release of MCP-1/CCL2, and the export of nuclear high-mobility group box 1; the effect abated in the presence of anti-CgA antibodies. The efficacy of the blockade was significantly correlated with the CgA concentration in the serum. The recombinant aminoterminal portion of CgA, corresponding to residues 1-78, had similar inhibitory effects on endothelial cells challenged with TNF-␣. Our results suggest that enhanced levels of CgA identify patients with extra-articular involvement and reveal a negative feedback loop that limits the activation of endothelial cells in RA.
2020
1Division of Rheumatology and 2Intensive Care Unit, Department of Medicine; 3Department of Laboratory Medicine; 4Department of Sports Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 5Corgenix Inc., Broomfield, CO, USA; 6Okayama University Graduate School of Medicine, Okayama, Japan; 7Third Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary; 8Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
Clinical Rheumatology, 2008
Considerable evidence indicates that patients with rheumatoid arthritis (RA) are at greater risk of developing atherosclerosis and cardiovascular disease. Recent studies support the predictive ability of endothelial function measures for subsequent atherosclerotic events. We have investigated the effects of infliximab, a chimeric monoclonal anti-tumor necrosis factor (TNF) antibody, on endothelial vasodilation, measured by brachial ultrasonography and on the levels of inflammatory biomarkers and adhesion molecules in ten consecutive patients with severe long-standing RA, despite methotrexate therapy, during the loading phase of infliximab therapy. Flow-mediated dilation (FMD) in RA patients at baseline was significantly impaired compared with healthy controls (7.71 ± 2.78% vs 14.91 ± 6.41%; p = 0.008) and improved significantly after infliximab infusion (12.63 ± 1.63% vs 7.71 ± 2.78%; p = 0.005). At baseline, a statistically significant correlation between C-reactive protein levels and FMD was found (r = −0.69, p = 0.026). However, this improvement was transitory, as FMD values returned to baseline values before each infliximab infusion at weeks 2, 6 and 14. There were no significant differences in baseline brachial artery diameter between visits, although at each time, the diameter was increased. According to European League Against Rheumatism response criteria, all ten patients were good responders. No significant differences were observed in intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, vascular endothelial growth factor and E-selectin plasma levels before and after each infusions. This study demonstrates that endothelial dysfunction is a reversible phenomenon in RA. The addition of anti-TNFα treatment reduces inflammatory symptoms in patients with severe RA. The improvement of endothelial function during the loading phase of therapy is transitory, suggesting an enhanced and persistent TNF-α generation within the arterial wall.
Linking systemic angiogenic markers to synovial vascularization in rheumatoid arthritis
PLOS ONE
Background Neoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularization. Objective To explore the associations between a set of complementary circulating angiogenic markers and a comprehensive US assessment in patients with RA.
Rheumatology, 2005
Vascular pathology, in the form of angiogenesis, is important in the perpetuation of rheumatoid arthritis (RA) and, in the form of endothelial dysfunction, contributes to associated cardiovascular co-morbidity. Emerging evidence suggests that TNFα blockade may modify vascular pathology in RA. Serum concentrations of vascular endothelial growth factor (VEGF), a potent endothelial cell-specific growth factor that is up-regulated by pro-inflammatory cytokines and by hypoxia, are elevated in RA and correlate with disease ...
The potential role of angiogenic factors in rheumatoid arthritis
International Journal of Rheumatic Diseases, 2014
Angiogenesis is an important phenomenon in the pathogenesis of some diseases, such as numerous types of tumors and autoimmunity, and also a number of soluble and cell-bound factors may stimulate neovascularization in inflammatory reaction processes. Here, by highlighting the significance of angiogenesis reaction in rheumatoid arthritis (RA), we will mainly focus on the role of various growth factors, cytokines, enzymes, cells, hypoxic conditions and transcription factors in the angiogenic process and we will then explain some therapeutic strategies based on blockage of angiogenesis and modification of the vascular pathology in RA.
2010-Rheumatology-NGF OCJ-Walsh-1852-61.pdf
Objectives. The osteochondral junction can be a source of pain in both RA and OA. Growth of blood vessels and nerves from the subchondral bone into articular cartilage may mediate the association between joint pathology and symptoms. We have investigated associations between angiogenesis, inflammation and neurovascular growth factor expression at the osteochondral junction in human arthritis.