TY - JOUR
T1 - Increased circulating concentrations of the counteradhesive proteins SPARC and thrombospondin-1 in systemic sclerosis (scleroderma). Relationship to platelet and endothelial cell activation
AU - Macko, Richard F.
AU - Gelber, Allan C.
AU - Young, Bradford A.
AU - Lowitt, Mark H.
AU - White, Barbara
AU - Wigley, Fredrick M.
AU - Goldblum, Simeon E.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - 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, β-thromboglobulin (βTG), and platelet factor 4 (PF4), 2 distinct platelet α-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 βTG (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 α-granule release in SSc patients. Plasma levels of BTG, PF4, and E-selectin were each similarly elevated (p < 0.003) in patients with both limited and diffuse SSc compared to controls. Conclusion. 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.
AB - 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, β-thromboglobulin (βTG), and platelet factor 4 (PF4), 2 distinct platelet α-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 βTG (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 α-granule release in SSc patients. Plasma levels of BTG, PF4, and E-selectin were each similarly elevated (p < 0.003) in patients with both limited and diffuse SSc compared to controls. Conclusion. 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.
KW - E-selectin
KW - Sparc
KW - Systemic sclerosis
KW - Thrombospondin-1 platelet factor 4
KW - β-Thromboglobulin
UR - http://www.scopus.com/inward/record.url?scp=0036897408&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036897408&partnerID=8YFLogxK
M3 - Article
C2 - 12465153
AN - SCOPUS:0036897408
SN - 0315-162X
VL - 29
SP - 2565
EP - 2570
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 12
ER -