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.