Circulating angiopoietin and Tie-2 levels in systemic sclerosis

Abstract

To determine the potential effects of angiopoietins Ang-1 and Ang-2 and their receptor Tie-2 in patients with systemic sclerosis (SSc). Twenty-six patients with limited SSc (l-SSc) and fourteen patients with diffuse SSc (d-SSc) were evaluated and compared to age-matched controls. Plasma levels of soluble sAng-1, sAng-2, sTie-2, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and endostatin were measured. Associations between these factors and clinical parameters were assessed. Levels of circulating factors and the ratios sAng-2/sAng-1 and sAng-2/sTie-2 were not different between l-SSc and d-SSc cases but were collectively higher compared to their controls: sAng-1 (p = 0.0108); sAng-2 (p < 0.0001); sTie-2 (p < 0.0001); endostatin (p < 0.0001), PlGF (p < 0.0001); VEGF (p = 0.0006); sAng-2/sAng-1 (p < 0.0001); sAng-2/sTie-2 (p < 0.0001). Concerning significant correlations among the angiopoietins and Tie-2, sAng-2 associated with sTie-2 (Spearman r = 0.47, p = 0.0155) in l-SSc only. sAng-1 did not show statistically significant correlations with any of the clinical variables, but sAng-2 did between PAP (r = 0.51, p = 0.0148) and predicted DLCO (r = -0.31, p = 0.0242) in l-SSc cases. sTie-2 negatively correlated with disease duration in l-SSc (r = -0.55, p = 0.0049). The sAng-2/sTie-2 ratio shows a positive association with disease activity in both l-SSc (r = 0.50, p = 0.0547) and d-SSc (r = 0.60, p = 0.0317). Levels of sAng-1, sAng-2 and sTie-2 are higher in SSc cases suggesting a pro-inflammatory state in an active endothelium. The near doubling of the sAng-2/sTie-2 ratio in SSc cases compared to controls suggests a shift toward vascular regression and angiostasis perhaps caused by Ang-2 blocking the action of Tie-2.