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


CONCLUSIONS
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.
Clavel
Gaëlle
G
Inserm, ERI 18, Bobigny, France.
Bessis
Natacha
N
Lemeiter
Delphine
D
Fardellone
Patrice
P
Mejjad
Othmane
O
Ménard
Jean-Francois
JF
Pouplin
Sophie
S
Boumier
Patrick
P
Vittecoq
Olivier
O
Le Loët
Xavier
X
Boissier
Marie-Christophe
MC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000097:blood*; D001168:Arthritis / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000276:immunology; D011859:Radiography; D040262:Receptors, Vascular Endothelial Growth Factor / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D042683:Angiopoietin-1; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1