Systemic lupus erythematosus patients exhibit functional deficiencies of endothelial progenitor cells

Systemic lupus erythematosus patients exhibit functional deficiencies of endothelial progenitor cells
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DOI:
10.1093/rheumatology/ken286
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发表时间:
2008-10-01
期刊:
影响因子:
5.5
通讯作者:
Smolen, J. S.
Smolen, J. S.
中科院分区:
医学1区
文献类型:
--
作者:
Grisar, J.;Steiner, C. W.;Smolen, J. S.

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目标。SLE的特点是心血管风险增加。由于内皮祖细胞(EPCs)已被描述为心血管风险的生物标志物,并且已知在各种疾病中耗尽,我们感兴趣的是SLE是否也与外周EPC水平改变或这些细胞的功能异常有关。通过FACS分析和菌落形成单位(CFU)测定,对31例不同疾病活度的SLE女性患者和年龄匹配的健康对照(hc)的EPCs进行了定量分析。此外,还测试了EPC的粘附能力和迁移能力。通过FACS(淋巴细胞门内0.045 +/- 0.006% vs 0.036 +/- 0.007%)和CFU测定(18 +/- 3 vs 15 +/- 2菌落/孔)评估,HC和SLE的EPC水平相似。与疾病活动度无相关性,但使用氯喹的SLE患者EPC水平显著降低(未使用氯喹的患者EPC水平为0.058 +/- 0.005%,而使用氯喹的患者EPC水平为0.024 +/- 0.008%,P < 0.05)。在体外培养中加入氯喹也导致SLE和HC的菌落形成减少。在检测EPC对人脐静脉内皮细胞(HUVEC)的粘附和迁移能力时,SLE患者细胞的粘附能力(19.2 +/- 3.5% vs 36.6 +/- 5.2% EPC/高倍视野,P < 0.02)和迁移能力(SLE患者56 +/- 6个细胞/随机显微镜视野,对照组121 +/- 28个细胞/随机显微镜视野,P < 0.02)降低。数据显示,EPCs在SLE中受到显著影响。虽然循环EPC水平在HC范围内,但它们表现出功能缺陷,可能导致组织可用性受损。
Objective. SLE is characterized by an increased cardiovascular risk. Since endothelial progenitor cells (EPCs) have been described to serve as a biomarker for the CV risk and are known to be depleted in various diseases, we were interested if SLE would also be associated with altered peripheral EPC levels or functional abnormalities of these cells.Methods. EPCs were quantified in 31 female SLE patients with different disease activity and in age-matched healthy controls (HCs) by FACS analysis and by colony forming unit (CFU) assay. Furthermore, EPC adhesion and migration capacity were tested.Results. EPC levels were similar in HC and SLE when assessed by FACS (0.045 +/- 0.006% vs 0.036 +/- 0.007% within the lymphocyte gate) and by the CFU assay (18 +/- 3 vs 15 +/- 2 colonies/well). No correlation with disease activity could be observed, but SLE patients treated with chloroquine exhibited significantly decreased EPC levels (0.058 +/- 0.005% without vs 0.024 +/- 0.008% with chloroquine, P < 0.05). Addition of chloroquine to in vitro cultures also led to a decreased colony formation in SLE and in HC. When testing the adhesion and migration capacity of EPC on human umbilical vein endothelial cells (HUVEC), cells from SLE patients had reduced adhesion (19.2 +/- 3.5% vs 36.6 +/- 5.2% EPC/high power field, P < 0.02) and migratory activity (56 +/- 6 cells/random microscopic field in SLE vs 121 +/- 28 in controls, P < 0.02).Conclusion. The data reveal that EPCs are significantly affected in SLE. While circulating EPC levels are in the range of HC, they exhibit functional deficiencies that may lead to impaired tissue availability.