Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very early arthritis and their association with inflammation and joint destruction

Abstract Objective: To investigate the involvement of angiogenesis markers in very early arthritis patients and their relevance to predict further joint destruction. Methods: Levels of Vascular Endothelial Growth Factor (VEGF), angiopoietin-1 (Ang-1), and soluble Fms-like tyrosine kinase-1 (sFlt-1) were measured by ELISA in serum samples from 310 patients having polyarthritis, evolving for less than 6 months (VErA cohort). Each angiogenesis marker was measured at baseline and one year later. X-rays of hands and feet were carried out at inclusion and after 1 year and read using the van der Heidje-modified Sharp method. Results: At baseline and after 1 year, VEGF levels were correlated with clinical and biological parameters of inflammation. We also observed a positive correlation between sFlt-1 levels and biological inflammation (Erythrocyte Sedimentation Rate (ESR): r = 0.17, p = 0.006; C Reactive Protein: r = 0.14, p = 0.02). Angiopoietin-1 levels were correlated with ESR ( r = 0.12, p = 0.04). Interestingly, only VEGF levels measured at baseline were correlated with Disease Activity Score measured 1 year later. Relationship between angiogenesis markers and radiographic progression was also evaluated. VEGF and Ang-1 levels measured at inclusion were related with Sharp score after one year (VEGF: r = 0.21, p < 0.001; Ang-1: r = 0.24, p < 0.001; Spearman's test). Moreover, VEGF levels were higher in patients with radiographic progression ( p = 0.002). Conclusion: Serum concentrations of VEGF, sFlt-1 and angiopoietin-1 were correlated to parameters of inflammation and to bone destruction in early arthritis. These results contribute to demonstrate that angiogenesis reflects disease severity and angiogenesis markers might become a new useful tool to evaluate disease activity and to estimate outcome for patients with inflammatory arthritis.