Increased circulating concentrations of the counteradhesive proteins SPARC and thrombospondin-1 in systemic sclerosis (scleroderma). Relationship to platelet and endothelial cell activation.
Increased circulating concentrations of the counteradhesive proteins SPARC and thrombospondin-1 in systemic sclerosis (scleroderma). Relationship to platelet and endothelial cell activation.
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发表时间：
2002-12
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通讯作者：
R. Macko;A. Gelber;B. Young;M. Lowitt;B. White;F. Wigley;S. Goldblum
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作者：
R. Macko;A. Gelber;B. Young;M. Lowitt;B. White;F. Wigley;S. Goldblum
目的探讨硬皮病患者外周血中抗粘附蛋白TSP-1和血小板反应蛋白TSP-1的浓度是否升高。研究了这些抗粘附蛋白与血小板和内皮细胞活化指标的关系。方法对45例SSc患者（26例局限型，19例弥漫型）和22例年龄和性别匹配的对照者的血浆进行了抗血小板抗体、TSP-1、β-血小板球蛋白（betaTG）、血小板因子4（PF 4）（两种不同的血小板α-颗粒产物）和可溶性E-选择素（内皮细胞活化的标志物）的测定。结果：局限性SSc患者的平均（+/- SE）浓度（124.0 +/- 9.6 ng/ml）高于对照组（66.8 +/- 8.0 ng/ml）（p = 0.0005），而弥漫性SSc患者的平均（+/- SE）浓度（74.1 +/- 7.9 ng/ml）则不然。在有限的SSc组中升高的血小板浓度不能归因于血小板或内皮细胞活化。与对照组（n = 11）相比，SSc患者（n = 29）的TSP-1浓度也增加（2.98 +/- 0.12 vs 2.4 +/- 0.21 log转换ng/ml; p < 0.02）。与血小板减少性紫癜不同，TSP-1浓度与β TG（r = 0.57，p = 0.0014）和PF 4（r = 0.41，p = 0.026）水平相关，表明TSP-1升高部分可通过SSc患者血小板α颗粒释放升高来解释。与对照组相比，局限性和弥漫性SSc患者的β TG、PF 4和E-选择素的血浆水平均相似地升高（p < 0.003）。结论SSc患者循环中TNF-α和TSP-1水平升高，提示调节血管组织结构和重塑的抗粘附蛋白可能参与SSc血管病变的发病机制。
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. 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.