title: Increased circulating concentrations of the counteradhesive proteins SPARC and thrombospondin-1 in systemic sclerosis (scleroderma). Relationship to platelet and endothelial cell activation.
abstract: OBJECTIVE
  To determine whether circulating concentrations of the counteradhesive proteins SPARC (secreted protein acidic and rich in cysteine) and thrombospondin-1 (TSP-1) are elevated in scleroderma (systemic sclerosis, SSc). The relationship of these counteradhesive proteins to measures of platelet and endothelial cell activation was examined.
  
  
  METHODS
  Plasma from 45 patients with SSc (26 limited form, 19 diffuse) and 22 age and sex matched controls was assayed for SPARC, TSP-1, beta-thromboglobulin (betaTG), and platelet factor 4 (PF4), 2 distinct platelet a-granule products, and soluble E-selectin, a marker of endothelial cell activation.
  
  
  RESULTS
  The mean (+/- SE) SPARC concentration was greater in patients with limited SSc (124.0 +/- 9.6 ng/ml) compared to controls (66.8 +/- 8.0 ng/ml) (p = 0.0005), whereas in patients with diffuse SSc (74.1 +/- 7.9 ng/ml) it was not. Elevated SPARC concentrations in the limited SSc group could not be ascribed to either platelet or endothelial cell activation. TSP-1 concentrations were also increased in SSc patients (n = 29) compared to controls (n = 11) (2.98 +/- 0.12 vs 2.4 +/- 0.21 log transformed ng/ml; p < 0.02). Unlike SPARC, TSP-1 concentrations correlated with both betaTG (r = 0.57, p = 0.0014) and PF4 (r = 0.41, p = 0.026) levels, indicating that increased TSP-1 could, in part, be explained through elevated platelet a-granule release in SSc patients. Plasma levels of betaTG, PF4, and E-selectin were each similarly elevated (p < 0.003) in patients with both limited and diffuse SSc compared to controls.
  
  
  CONCLUSIONS
  That circulating SPARC and TSP-1 are elevated in patients with SSc raises the possibility that counteradhesive proteins, which regulate vascular organization and remodeling, might contribute to the pathogenesis of SSc vasculopathy.
authors.affiliation: Department of Neurology, VA Maryland Health Care Center, Baltimore 21201, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Macko
authors.forename: Allan C
authors.initials: AC
authors.lastname: Gelber
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Young
authors.forename: Mark H
authors.initials: MH
authors.lastname: Lowitt
authors.forename: Barbara
authors.initials: B
authors.lastname: White
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
authors.forename: Simeon E
authors.initials: SE
authors.lastname: Goldblum
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015676:Osteonectin / Q000097:blood*; D015539:Platelet Activation; D010978:Platelet Factor 4 / Q000032:analysis; D012595:Scleroderma, Systemic / Q000097:blood*; D019700:Thrombospondin 1 / Q000097:blood*; D001620:beta-Thromboglobulin / Q000032:analysis
chemical_list: D019040:E-Selectin; D015676:Osteonectin; D019700:Thrombospondin 1; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4