- Original article
- Open Access
Baseline angiopoietin-2/angiopoietin-1 (Ang2/Ang1) ratio is correlated with the synovial vascularity measured 1 month later in rheumatoid arthritis
Egyptian Rheumatology and Rehabilitation volume 40, pages 193–197 (2013)
Synovial angiogenesis is a component of rheumatoid pannus and considered to be an important early step in the pathogenesis of rheumatoid arthritis (RA).
The aim of this study was to evaluate the serum levels of angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), as well as the significance of the Ang2/Ang1 ratio in RA in relation to the joints’ blood flow signals and RA activity parameters. In addition, we studied their relevance in predicting the state of angiogenesis.
Patients and methods
This study was carried out on 65 consecutive very early RA patients. Power Doppler ultrasonography was performed in a total of 10 joints. The blood flow signals of each joint were scored on a three-grade scaling system. The total of the scores of the 10 joints was defined as the total signal score (TSS). On the same day, serum variables including vascular endothelial growth factor (VEGF), Ang1 and Ang2 levels, and clinical disease activity were evaluated. All the parameters measured were reassessed after 1 month.
Serum VEGF, Ang2 levels, and Ang2/Ang1 ratio were significantly correlated with C-reactive protein, DAS28-CRP, and TSS at baseline and after 1 month. Moreover, significant correlations were observed between serum VEGF and Ang2 levels and Ang2/Ang1 ratio both at baseline and 1 month later. Interestingly, baseline serum VEGF level and Ang2/Ang1 ratio were significantly correlated with TSS after 1 month.
Serum concentrations of VEGF and Ang2 as well as Ang2/Ang1 ratio were correlated with parameters of inflammation in early RA. Elevated serum VEGF and Ang2/Ang1 ratio (in favor of Ang2) could reflect a phase of vigorous angiogenesis.
Schrieber L, Jackson JC. In: Klippel HJ, Dieppe PA, editors. Angiogenesis in rheumatoid arthritis. Rheumatology 2nd ed. London, UK: Mosby International; 1988. 12.1–12.4.
Koch AE, Volin MV, Woods JM, Kunkel SL, Connors MA, Harlow LA, et al. Regulation of angiogenesis by the C-X-C chemokines, interleukin-8 and epithelial neutrophil activating peptide 78 in the rheumatoid joint. Arthritis Rheum 2001; 44:31–40.
Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 1999; 286:2511–2514.
Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997; 277:55–60.
Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature 2000; 407:242–248.
Scharpfenecker M, Fiedler U, Reiss Y, Augustin HG. The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. J Cell Sci 2005; 118:771–780.
Roviezzo F, Tsigkos S, Kotanidou A, Bucci M, Brancaleone V, Cirino G, et al. Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. J Pharmacol Exp Ther 2005; 314:738–744.
Funovits J, Aletaha D, Bykerk V, Combe B, Dougados M, Emery P, et al. The 2010 American College of Rheumatology/European league against rheumatism classification criteria for rheumatoid arthritis: methodological report phase I. Ann Rheum Dis 2010; 69:1589–1595.
Fransen J, Welsing P, Keijzer RD, Riel PV. Disease activity scores using C-reactive protein: CRP may replace ESR in the assessment of RA disease activity. Ann Rheum Dis 2004; 62:151.
Ellegaard K, Christensen R, Torp Pedersen S, Terslev L, Holm CC, Kønig MJ, et al. Ultrasound Doppler measurements predict success of treatment with anti-TNF-α drug in patients with rheumatoid arthritis: a prospective cohort study. Rheumatology 2011; 50:506–512.
Seymour MW, Kelly S, Beals CR, Malice MP, Bolognese JA, Dardzinski BJ, et al. Ultrasound of metacarpophalangeal joints is a sensitive and reliable endpoint for drug therapies in rheumatoid arthritis: results of a randomized, two-center placebo-controlled study. Arthritis Res Ther 2012; 14:R198.
Ballara S, Taylor PC, Reusch P, Marmé D, Feldmann M, Maini RN, et al. Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum 2001; 44:2055–2064.
Clavel G, Bessis N, Lemeiter D, Fardellone P, Mejjad O, Ménard JF, et al. Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very early arthritis and their association with inflammation and joint destruction. Clin Immunol 2007; 124:158–164.
Kurosaka D, Hirai K, Nishioka M, Miyamoto Y, Yoshida K, Noda K, et al. Clinical significance of serum levels of vascular endothelial growth factor, angiopoietin-1 and angiopoietin-2 in patients with rheumatoid arthritis. J Rheumatol 2010; 37:1121–1128.
Strunk J, Heinemann E, Neeck G, Schmidt KL, Lange U. A new approach to studying angiogenesis in rheumatoid arthritis by means of power Doppler ultrasonography and measurement of serum vascular endothelial growth factor. Rheumatology 2004; 43:1480–1483.
Walther M, Harms H, Krenn V, Radke S, Faehndrich TP, Gohlke F. Correlation of power Doppler sonography with vascularity of the synovial tissue of the knee joint in patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum 2001; 44:331–338.
Szekanecz Z, Koch AE. Mechanisms of disease: angiogenesis in inflammatory diseases. Nat Clin Pract Rheumatol 2007; 3:635–643.
Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, et al. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 1996; 87:1161–1169.
Shahrara S, Volin MV, Connors MA, Haines GK, Koch AE. Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue. Arthritis Res 2002; 4:201–208.
About this article
Cite this article
Senna, M.K., Machaly, S.A., Foda, M. et al. Baseline angiopoietin-2/angiopoietin-1 (Ang2/Ang1) ratio is correlated with the synovial vascularity measured 1 month later in rheumatoid arthritis. Egypt Rheumatol Rehabil 40, 193–197 (2013). https://doi.org/10.4103/1110-161X.123797
- power Doppler ultrasonography
- rheumatoid arthritis
- vascular endothelial growth factor