Andrigueti Fernando V, Arismendi Maria I, Ebbing Pâmela C C, Kayser Cristiane
Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Microvasc Res. 2015 Mar;98:82-7. doi: 10.1016/j.mvr.2015.01.004. Epub 2015 Jan 13.
Microangiopathy and endothelial dysfunction are present in the early stages of systemic sclerosis (SSc). Defective vasculogenesis mediated by bone marrow-derived endothelial progenitor cells (EPCs) might be involved in the vascular abnormalities found in SSc.
To evaluate the circulating EPC levels and EPC subtypes via flow cytometry and early outgrowth colony-forming units (CFUs) in patients with SSc compared to healthy subjects.
Thirty-nine female SSc patients (30 in the early stages of SSc) and 44 age-matched healthy women were included. Peripheral blood EPCs were quantified using flow cytometry and by counting the early outgrowth CFUs.
The EPCs quantified with flow cytometry and the CFU numbers were significantly lower in SSc patients than in control subjects (155.1 ± 95.1 vs. 241.3 ± 184.2 EPC/10(6) lymphomononuclear cells, p=0.011; 15.4 ± 8.6 vs. 23.5 ± 10.9 CFU, p<0.001; respectively), as well as in the group of patients in the early stages of SSc compared to the controls. Patients with digital ulcers had significantly higher CFU counts than those without ulcers (p=0.013). Among patients with the scleroderma pattern on nailfold capillaroscopy, patients with the late pattern had significantly lower EPC levels than those with the early and active patterns (p=0.046). There were no significant correlations of EPCs or CFU levels with RP duration.
The present study revealed decreased EPCs in SSc patients, including those with early disease onset. These findings suggest that defective vasculogenesis occurs in the early phases of the disease. Therefore, EPCs might be an important therapeutic target for the prevention of vascular complications in SSc patients.
微血管病变和内皮功能障碍存在于系统性硬化症(SSc)的早期阶段。骨髓源性内皮祖细胞(EPCs)介导的血管生成缺陷可能与SSc中发现的血管异常有关。
通过流式细胞术和早期集落形成单位(CFUs)评估SSc患者与健康受试者相比循环EPC水平和EPC亚型。
纳入39名女性SSc患者(30名处于SSc早期)和44名年龄匹配的健康女性。使用流式细胞术并通过计数早期集落形成CFUs对外周血EPCs进行定量。
SSc患者中通过流式细胞术定量的EPCs和CFU数量显著低于对照组(分别为155.1±95.1对241.3±184.2个EPC/10(6)淋巴细胞单核细胞,p=0.011;15.4±8.6对23.5±10.9个CFU,p<0.001),与对照组相比,SSc早期患者组也是如此。有指端溃疡的患者CFU计数显著高于无溃疡患者(p=0.013)。在甲襞毛细血管镜检查有硬皮病样改变的患者中,晚期改变的患者EPC水平显著低于早期和活动期改变的患者(p=0.046)。EPCs或CFU水平与雷诺现象持续时间无显著相关性。
本研究揭示了SSc患者,包括疾病早期发病患者的EPCs减少。这些发现表明在疾病早期阶段发生了血管生成缺陷。因此,EPCs可能是预防SSc患者血管并发症的重要治疗靶点。