Angiopoietins-1 and -2 are differentially expressed in the sera of patients with systemic sclerosis: high angiopoietin-2 levels are associated with greater severity and higher activity of the disease

Rheumatology (Oxford). 2011 Apr;50(4):746-55. doi: 10.1093/rheumatology/keq392. Epub 2010 Dec 10.

Abstract

Objectives: The aim of the study was to investigate serum concentration of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in SSc patients and to correlate Ang-1 and -2 levels with clinical manifestations.

Methods: Serum levels of Ang-1 and -2 were determined by ELISA in 47 SSc patients and 27 healthy controls matched for age and sex.

Results: In SSc patients, Ang-1 was significantly lower [mean (s.d.): 21,666.09 (11,516.06) pg/ml], while Ang-2 was significantly increased [2739.60 (1009.25) pg/ml] when compared with the control group [Ang-1: 28607.13 (10,506.93) pg/ml; Ang-2: 1706.28 (556.28) pg/ml, P < 0.01, for both comparisons]. No correlation was observed between Ang-1 and -2 levels. Serum concentrations of Ang-2 correlated with the modified Rodnan skin score (P < 0.01, r =0.422), the European Scleroderma Study Group (EScSG) disease activity index score (P < 0.001, r =0.403), ESR (P < 0.05, r = 0.366) and CRP concentration (P < 0.05, r =0.292), and showed inverse correlation with diffusing capacity for carbon monoxide (DL(CO)) (P < 0.01, r = -0.281). Ang-2 was significantly increased in SSc patients with more advanced capillary damage, as indicated by the presence of late capillaroscopic pattern, than in those with less severe microangiopathy (active pattern), and in SSc patients with intermediate/late stage of disease than in SSc subjects with early disease. In multivariate regression analysis, Ang-2 was independently associated with the EScSG activity index [β-coefficient (β = 0.305, P= 0.038], ESR (β= 0.390, P =0.006) and, inversely, with the presence of digital ulcers (β =-0.426, P = 0.003).

Conclusions: Differential expression of Ang-1/Ang-2 might contribute to the pathogenesis of SSc. Ang-2 might be a new biomarker of disease activity in SSc.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiopoietin-1 / blood*
  • Angiopoietin-2 / blood*
  • Biomarkers / blood
  • Blood Sedimentation
  • Capillaries / physiopathology
  • Carbon Monoxide / blood
  • Case-Control Studies
  • Disability Evaluation*
  • Female
  • Humans
  • Middle Aged
  • Nails / blood supply
  • Regression Analysis
  • Scleroderma, Systemic / blood*
  • Scleroderma, Systemic / diagnosis
  • Scleroderma, Systemic / physiopathology*
  • Severity of Illness Index*

Substances

  • Angiopoietin-1
  • Angiopoietin-2
  • Biomarkers
  • Carbon Monoxide