A fresh look at angiogenesis in juvenile idiopathic arthritis

Abstract

Angiogenesis is the complex process of creating new capillaries from preexisting blood vessels due to hypoxemia, injury or inflammation of the tissues. Numerous cytokines and cell mediators have been identified to induce and stimulate angiogenesis, but vascular endothelial growth factor (VEGF) is a key regulator. The role of proangiogenic factors in the pathogenesis of chronic arthritis is currently a subject of intensive investigations in adult patients with rheumatoid arthritis (RA) and, to a limited extent, in children with juvenile idiopathic arthritis (JIA). Recent studies has shown a significant correlation between proangiogenic marker concentrations and the severity of inflammation in either RA or JIA patients. The serum neovascularization markers correlate with the power Doppler ultrasound image of the inflamed joint and hypertrophic synovium, which may be connected with the disease activity.The aim of this paper is to describe the state of the art on the important role of angiogenesis in adult and childhood rheumatoid arthritis.

Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches

“…Hyperplasia and hypertrophy of the synovium causes intraarticular hypoxia, increasing the production of pro-angiogenic mediators and initiating pathological angiogenesis [ 12 ]. Increased concentrations of vascular endothelial growth factor (VEGF), a potent endothelial cell (EC) mitogen, its soluble receptors-1 and -2 (sVEGF-R1, sVEGF-R2), and osteopontin (OPN), a chemotactic factor that activates mononuclear cells, have been correlated to synovial angiogenesis assessed by Doppler ultrasonography of JIA patients [ 12 ]. Angiopoietin-1 (Ang-1), another pro-angiogenic EC mitogen with a role in stabilisation of newly formed vessels was also shown to be upregulated in JIA.…”

Integrative Genetics Analysis of Juvenile Idiopathic Arthritis Identifies Novel Loci

“…Our hsGWAS results suggest additional subtypes of JIA patients could potentially benefit from the treatment of IL-1 and/or IL-6 blockade. The novel GWS association of SCUBE1 with several JIA subtypes implicates the critical role of angiogenesis in JIA pathogenesis 30,52 . Some anti-inflammatory drugs, such as anti-TNF, anti-IL-6, have dual roles in blocking both inflammation and angiogenesis 53,54 .…”

How Does Endothelial Permeability Affect the Development of Juvenile Idiopathic Arthritis? Vascular Endothelial Cadherin as a Promising New Tool Helpful in the Diagnostic Process

“…However, the authors were unable to measure VE-cadherin levels in synovial fluid in the recent study. As antiangiogenic therapy has become a promising novel perspective for the treatment of RA, clinical trials should consider not only anti-VEGF antibodies (such as bevacizumab and vatalanib) [ 27 ] but also drugs affecting VE-cadherin levels like tyrosine-kinase inhibitors (such as sunitinib) [ 10 ].…”