Background Many cytokines may potentially play a relevant role in the pathogenesis of different aspects of SSc, particularly fibrosis and endothelial injury. Some data suggest that substance P (SP) may act in an autocrine/paracrine manner to regulate vasoconstriction and/or immunologic and inflammatory responses. VEGF and MCP1, which are produced by inflammatory cells, may be involved in the pathogenesis of vascular changes and accumulation of extracellular matrix in SSc.
Objectives The aim of this study was to determine the expression of Substance P (SP), Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein-1 (MCP-1) in SSc patients and their relationship with the main clinical manifestations of disease
Methods 34 SSc patients fulfilling the 2013 ACR/EULAR criteria for SSc and classified according to Leroy as having limited cutaneous (lSSc) or diffuse cutaneous (dSSc) disease were recruited. 28 sex and age matched healthy subjects was used as control. For each recruited patient we analyzed the disease characteristic, including the extent of skin fibrosis, the pattern of internal organ involvement, the presence of digital ulcers (DU) and autoantibody profile. Peripheral Blood Mononuclear Cells (PBMCs) were isolated and cultured from both SSc patients and healthy controls. The expression of SP, VEGF, MCP1 was analyzed by real-time polymerase chain reaction (PCR) and their concentrations where measured in supernatants of cultured PBMCs using enzyme-linked immunosorbent assay (ELISA). The correlation between cytokine expression and clinical manifestations was evaluated
Results The results showed that the mRNA and the protein levels of SP and VEGF were significantly higher in SSc patients compared to controls (190,55±59,1pg/mL vs 128,85±69,8pg/mL and 422,31±149,4pg/mL vs 309,25pg/mL respectively, p<0,05); further, SP and VEGF levels were higher in dSSc compared to lSSc and correlated to disease duration. No difference was detected in MCP1 synthesis and expression between SSc subjects and healthy controls (507,17±153,9pg/mL vs 481,2±118,2 pg/mL) even if in dSSc patients a slight increase was observed. VEGF production negatively correlated with the prevalence of DU. No correlation between cytokines production and heart, lung and gastrointestinal involvement and autoantibody profile was found.
Conclusions The preliminary data of this study show that SP and VEGF are over-expressed in PBMCs of SSc subjects and are related to the extent of skin involvement, whereas only VEGF production negatively correlates with the prevalence of DU. The exact role played by SP and VEGF in the pathogenesis of vascular injury and fibrosis in SSc and their relationship with the immune abnormalities observed in this disease is not completely clear and the available data are contrasting. Additional in vitro and in vivo studies are needed to better understand the role of SP and VEGF in the pathogenesis of SSc.
Disclosure of Interest None declared
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