Abstract
Synovial angiogenesis is considered to be an important early step in the pathogenesis of juvenile idiopathic arthritis (JIA). In this study we assessed levels of angiogenic markers in serum or synovial fluid and their possible relevance to disease activity or degree of ultrasound signs of synovial inflammation and angiogenesis in early JIA. The concentration of vascular endothelial growth factor (VEGF), its soluble receptors 1 and 2 (sVEGF-R1, sVEGF-R2), and angiopoietins 1 and 2 (ANG-1, ANG-2) were evaluated in 43 JIA patients and 23 healthy controls. Synovial angiogenesis was assessed by means of Power-Doppler Ultrasonography (PDUS), according to the fourth-grade vascularity scale. VEGF and its receptors' (sVEGF-R1, sVEGF-R2) serum levels were significantly higher in JIA patients (p = 0.002). We found large variation in serum ANG-1 and ANG-2 levels. The PDUS imaging identified increased synovial microvascular blood flow in 15 (35.7%) examined JIA children. Intensity of joint vascularization correlated with higher serum VEGF and its levels was lowest in grade 0 and highest in grade 3 (p < 0.007 and p < 0.001, resp.). In conclusion, the high correlation between synovial microvascular blood flow, serum angiogenic proteins, and symptoms of synovitis may indicate its important role in pathogenesis of JIA.
Highlights
Juvenile idiopathic arthritis (JIA) is the most common childhood chronic rheumatic disease, characterized by arthritis of unknown origin with onset before the age of 16 years [1, 2]
Vascular endothelial growth factor (VEGF) serum levels were significantly higher in JIA patients than in healthy controls (p = 0.002, Table 2)
Serum levels of ANG-1 correlated with white blood cells (WBC) and platelets (PLT) counts (R = 0.31 and R = 0.55, resp.; p < 0.05), whereas ANG-2 correlated with WBC count (R = 0.32 and p < 0.05)
Summary
Juvenile idiopathic arthritis (JIA) is the most common childhood chronic rheumatic disease, characterized by arthritis of unknown origin with onset before the age of 16 years [1, 2]. The inflammatory process in JIA is characterized by excessive proliferation of synoviocytes It is strongly associated with a neovascularization due to increased metabolic requirement of hypertrophic synovium [3]. Neovascularization, defined as angiogenesis, is a complex process in which new capillaries develop from preexisting vasculature due to hypoxemia, injury, or inflammation of the tissues. This process plays a pivotal role in a number of physiological and pathological conditions, including chronic inflammatory diseases [4]. Angiopoietins (ANGs), less explored in the pathogenesis of chronic inflammatory connective tissue diseases, are known as the mediators of angiogenesis regulating endothelial integrity and inflammation
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