title: 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.
authors.affiliation: Department of Medicine, University of British Columbia, 700 West 57th Avenue, Vancouver, BC V6P 1S1, Canada. James.Dunne@VCH.ca
authors.forename: James V
authors.initials: JV
authors.lastname: Dunne
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Keen
authors.forename: Stephan F
authors.initials: SF
authors.lastname: Van Eeden
mesh_terms: D000328:Adult; D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D042787:Receptor, TIE-2 / Q000097:blood*; D012595:Scleroderma, Systemic / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D008565:Membrane Proteins; C098069:PIGF protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2