Increased circulating concentrations of the counteradhesive proteins SPARC and thrombospondin-1 in systemic sclerosis (scleroderma). Relationship to platelet and endothelial cell activation

Richard F. Macko, Allan Gelber, Bradford A. Young, Mark H. Lowitt, Barbara White, Fredrick Wigley, Simeon E. Goldblum

Research output: Contribution to journalArticle

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, 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.

Original languageEnglish (US)
Pages (from-to)2565-2570
Number of pages6
JournalJournal of Rheumatology
Volume29
Issue number12
StatePublished - Dec 1 2002

Fingerprint

Thrombospondin 1
Systemic Scleroderma
Cysteine
Blood Platelets
Endothelial Cells
Platelet Factor 4
Proteins
Diffuse Scleroderma
E-Selectin

Keywords

  • β-Thromboglobulin
  • E-selectin
  • Sparc
  • Systemic sclerosis
  • Thrombospondin-1 platelet factor 4

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Increased circulating concentrations of the counteradhesive proteins SPARC and thrombospondin-1 in systemic sclerosis (scleroderma). Relationship to platelet and endothelial cell activation. / Macko, Richard F.; Gelber, Allan; Young, Bradford A.; Lowitt, Mark H.; White, Barbara; Wigley, Fredrick; Goldblum, Simeon E.

In: Journal of Rheumatology, Vol. 29, No. 12, 01.12.2002, p. 2565-2570.

Research output: Contribution to journalArticle

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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, 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.",
keywords = "β-Thromboglobulin, E-selectin, Sparc, Systemic sclerosis, Thrombospondin-1 platelet factor 4",
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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

AU - Young, Bradford A.

AU - Lowitt, Mark H.

AU - White, Barbara

AU - Wigley, Fredrick

AU - Goldblum, Simeon E.

PY - 2002/12/1

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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.

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