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系统性硬化症患者的循环微粒体和血浆可溶性 E-及 P-选择素水平。

Circulating microparticles and plasma levels of soluble E- and P-selectins in patients with systemic sclerosis.

机构信息

Department of Dermatology, Bispebjerg Hospital, Copenhagen University Hospital , Copenhagen , Denmark.

出版信息

Scand J Rheumatol. 2013;42(6):473-82. doi: 10.3109/03009742.2013.796403. Epub 2013 Sep 9.

Abstract

OBJECTIVES

Microparticles (MPs) may be involved in the pathogenesis of systemic sclerosis (SSc), which includes vasculopathy, endothelial cell activation, and coagulation activation. Circulating MPs from SSc patients were characterized and their relationship with soluble markers of vascular activation investigated.

METHOD

This study included 121 SSc patients [79 with limited (lcSSc) and 42 with diffuse cutaneous SSc (dcSSc)] and 49 sex- and age-matched healthy controls (HCs). The MPs were characterized by flow cytometry for annexin V (AnxV)-binding capacity and their expression of surface markers of platelets (PMPs), leucocytes (LMPs), or endothelial cells (EMPs). Plasma levels of soluble (s) E- and P-selectins were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS

The total concentrations of MPs and of PMPs, LMPs, and EMPs were 22-42% lower in SSc patients than in HCs (p < 0.001). However, within the cell-derived MP pool, a 47% higher fraction of AnxV non-binding MPs (F-AnxV(-) MPs) was found in the SSc patients compared to the HCs (p < 0.05). The plasma levels of sE- and sP-selectins were increased by 47-64% in the SSc patients compared to HCs (p < 0.001). Multiple regression analysis showed that the raised plasma levels of sE- and sP-selectin were associated with F-AnxV(-) EMPs in dcSSc patients (p = 0.008 and p = 0.001, respectively) but not in lcSSc patients (p = 0.33 and p = 0.82, respectively).

CONCLUSIONS

While the total number of MPs was decreased, the number of F-AnxV(-) MPs increased in SSc patients. The F-AnxV(-) EMPs were associated with plasma levels of markers of vascular activation in patients with dcSSc.

摘要

目的

微粒(MPs)可能参与全身性硬皮病(SSc)的发病机制,其中包括血管病变、内皮细胞激活和凝血激活。对 SSc 患者的循环 MPs 进行了特征描述,并研究了它们与血管激活可溶性标志物的关系。

方法

本研究纳入了 121 名 SSc 患者[79 名局限性硬皮病(lcSSc)和 42 名弥漫性皮肤硬皮病(dcSSc)]和 49 名性别和年龄匹配的健康对照者(HCs)。通过流式细胞术检测 Annexin V(AnxV)结合能力和血小板(PMPs)、白细胞(LMPs)或内皮细胞(EMPs)表面标志物来对 MPs 进行特征描述。通过酶联免疫吸附试验(ELISA)测定血浆可溶性(s)E-和 P-选择素水平。

结果

与 HCs 相比,SSc 患者的 MPs 总浓度以及 PMPs、LMPs 和 EMPs 的浓度低 22-42%(p<0.001)。然而,在细胞来源的 MP 池中,SSc 患者的 AnxV 非结合 MPs(F-AnxV(-) MPs)比例比 HCs 高 47%(p<0.05)。与 HCs 相比,SSc 患者的血浆 sE-和 sP-选择素水平升高了 47-64%(p<0.001)。多元回归分析显示,dcSSc 患者血浆中升高的 sE-和 sP-选择素水平与 F-AnxV(-) EMPs 相关(p=0.008 和 p=0.001),而在 lcSSc 患者中无相关性(p=0.33 和 p=0.82)。

结论

尽管 MPs 的总数减少,但 SSc 患者的 F-AnxV(-) MPs 数量增加。在 dcSSc 患者中,F-AnxV(-) EMPs 与血管激活标志物的血浆水平相关。

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