The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis

Abstract

The pathological hallmarks of Systemic sclerosis (SSc) constitute an inter-related triad of autoimmunity, vasculopathy and tissue remodeling. Many signaling mediators have been implicated in SSc pathology; most focusing on individual components of this pathogenic triad and current treatment paradigms tend to approach management of such as distinct entities. The present review shall examine the role of vascular endothelial growth factor (VEGF) in SSc pathogenesis. We shall outline potential mechanisms whereby differential vascular endothelial growth factor-A (VEGF-A) isoform expression (through conventional and alternative VEGF-A splicing,) may influence the relevant burden of vasculopathy and fibrosis offering novel insight into clinical heterogeneity and disease progression in SSc. Emerging therapeutic approaches targeting VEGF signaling pathways might play an important role in the management of SSc, and differential VEGF-A splice isoform expression may provide a tool for personalized medicine approaches to disease management.

Impact of Human Cytomegalovirus and Human Herpesvirus 6 Infection on the Expression of Factors Associated with Cell Fibrosis and Apoptosis: Clues for Implication in Systemic Sclerosis Development

“…As regards cell-mediated immunity, a relevant role of T lymphocyte responses and pro-inflammatory cytokine aberrant production in the pathogenesis of SSc has been highlighted, with their possible contribution in the modulation of fibrosis and vascular damage [ 17 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Recent data from our group support the importance of HCMV specific CD8+ T cells, demonstrating a statistically significant association of HCMV-antigen driven CD8+ T cell responses in SSc patients with some of the most relevant disease parameters [ 16 ].…”

Matrix Metalloproteinases MMP-2 and MMP-9, Their Inhibitors TIMP-1 and TIMP-2, Vascular Endothelial Growth Factor and sVEGFR-2 as Predictive Markers of Ischemic Retinopathy in Patients with Systemic Sclerosis—Case Series Report

“…In our previous reports on the role of VEGF and its inhibitor soluble VEGF receptor-2 (sVEGFR-2), we have also shown that higher concentrations of proangiogenic factors may be found in the tears of patients with scleroderma compared with patients' blood serum and control group [15]. Some previous studies also indicate the major role of VEGF in angiogenesis in systemic sclerosis [32][33][34]. VEGF is involved in many different pathways of angiogenetic processes: initial vasodilation, remodeling of the perivascular matrix, and stimulation of proliferation of endothelial cells [35].…”

Vascular endothelial growth factor (VEGF)-A and VEGF-A165b are associated with time to remission of granulomatosis with polyangiitis in a nationwide Japanese prospective cohort study

“…25–27 Therapeutic modulation of VEGF-A 165 b is currently being investigated in cancer and angiogenic eye disorders and is being considered to be developed for treating the autoimmune disorder, systemic sclerosis. 28,29 Besides, several reports have described the involvement of VEGF-A in systemic vasculitis, such as GPA (previously known as Wegener’s granulomatosis), 30 giant cell arteritis 31 and Kawasaki disease. 32 Studies have shown the clinical value of VEGF-A in monitoring disease activity in vasculitis, including MPA.…”