Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis
Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis
复制标题
DOI：
10.1161/01.cir.0000151875.21836.ae
复制
发表时间：
2005-01-18
期刊：
影响因子：
37.8
通讯作者：
Smolen, JS
中科院分区：
文献类型：
--
作者：
Grisar, J;Aletaha, D;Smolen, JS
背景-风湿性关节炎（RA）的特点是心血管疾病发病率和死亡率增加，不能仅仅用传统的心血管危险因素来解释。心血管疾病的发病率与疾病活动有关，可以通过有效的治疗来恢复正常。由于内皮祖细胞（EPCs）在外周血中的数量与心血管疾病的风险呈负相关，我们研究了是否也可以观察到这种异常的RA患者。方法和结果- EPCs测定在52例RA患者和16名健康参考（HR）的荧光激活细胞分选（FACS）分析。患者分为活动性疾病组（n = 36）和低疾病活动性组（n = 16）。在淋巴细胞群中通过流式细胞术对CD 34/KDR/AC 133呈阳性的细胞被表征为EPC。此外，在患者亚组中，还通过集落形成单位（CFU）和循环血管生成细胞（CAC）测定来定量循环EPCs。流式细胞仪分析表明，活动期RA患者的内皮祖细胞数量显著低于高血压患者（分别为0.026 +/- 0.002%和0.045 +/-0.008%，P < 0.05），CFU测定（HR中5 +/-2对18 +/-5CFU/孔的平均值，P < 0.05）和CAC测定（7 +/-2对52 +/-16阳性细胞/高倍视野的平均值，P < 0.005）。相反，来自低疾病活动性患者的循环EPC的频率与健康个体的循环EPC的频率（通过FACS分析为0.052 +/-0.006%）、CFU测定（10 +/-5 CFU/孔）和CAC测定（平均25 +/-5阳性细胞）相当。此外，外周血中的EPC数量与疾病活动性评分评估的疾病活动性呈负相关（r =-0.38，P < 0.01）。这可能是导致RA心血管风险增加的几个因素之一。
Background - Rheumatoid arthritis (RA) is characterized by increased cardiovascular morbidity and mortality that cannot be explained solely by traditional cardiovascular risk factors. Cardiovascular morbidity is related to disease activity and can be normalized by effective therapy. Because the quantity of endothelial progenitor cells (EPCs) in the peripheral blood is correlated inversely with cardiovascular risk, we studied whether such abnormalities could also be observed in patients with RA.Methods and Results - EPCs were determined in 52 RA patients and in 16 healthy referents (HRs) by fluorescence-activated cell-sorting (FACS) analysis. Patients were divided into groups characterized by active disease (n = 36) and low disease activity ( n = 16). Cells that were positive by flow cytometry for CD34/KDR/AC133 within the lymphocyte population were characterized as EPCs. Furthermore, in subgroups of patients, circulating EPCs were also quantified by a colony-forming unit (CFU) and a circulating angiogenic cell (CAC) assay. EPCs were significantly decreased in RA patients suffering from active disease compared with those from HRs, as measured by FACS analysis (0.026 +/- 0.002% versus 0.045 +/- 0.008%, respectively, P < 0.05), CFU assay ( mean of 5 +/- 2 versus 18 +/- 5 CFU/well in HRs, P < 0.05), and CAC assay ( mean of 7 +/- 2 versus 52 +/- 16 positive cells/high-power field, P < 0.005). In contrast, the frequency of circulating EPCs from patients with low disease activity was comparable to that of healthy individuals (0.052 +/- 0.006% by FACS analysis), CFU assay (10 +/- 5 CFU/well), and CAC assay (mean of 25 +/- 5 positive cells). Moreover, EPC quantities in peripheral blood were correlated inversely with disease activity as assessed by the disease activity score (r = - 0.38, P < 0.01).Conclusions - Our observations indicate that active RA is associated with a depletion of circulating EPCs. This might be one of several factors contributing to the increased cardiovascular risk in RA.