Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis
Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis
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DOI：
10.1002/art.21899
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发表时间：
2006-06-01
影响因子：
--
通讯作者：
Ikeda, Yasuo
中科院分区：
文献类型：
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作者：
Kuwana, Masataka;Kaburaki, Junichi;Ikeda, Yasuo
Objective.评价阿托伐他汀是否能增加系统性硬化症（SSc;硬皮病）患者的骨髓源性循环内皮前体细胞（CEP）并改善血管症状。该研究设计为开放标签、前瞻性研究，涉及14例SSc患者，这些患者接受10 mg/天阿托伐他汀治疗12周，并在随后4周进行随访。在第0周（治疗前）、第4周、第8周、第12周（治疗期间）和第16周（治疗后）通过细胞分选，然后通过3色流式细胞术定量CEP。雷诺现象变量，整体措施，心理量表以及循环血管生成因子和内皮活化/损伤标记物进行了系列评估。CEPs分化为成熟内皮细胞的潜力在血管生成刺激的培养中进行了检测。所有患者均未发生不良事件，但1例患者因血清总胆固醇过度降低而退出研究。阿托伐他汀治疗导致CEP较基线水平增加1.7- 8.0倍（P < 0.0001），但在治疗后这些数字恢复到基线水平。然而，8例患者（62%）的CEP数量逐渐减少，即使在服用阿托伐他汀期间。阿托伐他汀治疗期间，雷诺现象程度的变量显著改善，血管生成因子和血管内皮活化/损伤标记物的上调水平显著降低。这些变量在停药后恢复到基线水平。相反，阿托伐他汀不能提高CEPs的体外成熟潜能。这项初步研究的结果表明，阿托伐他汀治疗可以增加CEP，并可能有效地改善雷诺现象，即使在SSc患者谁有CEP功能障碍的本质。
Objective. To evaluate whether atorvastatin can increase bone marrow-derived circulating endothelial precursors (CEPs) and improve the vascular symptoms in patients with systemic sclerosis (SSc; scleroderma).Methods. The study was designed as an open-label, prospective study involving 14 patients with SSc who received 10 mg/day of atorvastatin for 12 weeks and were followed up for the subsequent 4 weeks. CEPs were quantified at weeks 0 (pretreatment), 4, 8, 12 (during treatment), and 16 (posttreatment) by cell sorting followed by 3-color flow cytometry. Raynaud's phenomenon variables, global measures, and psychological scales as well as circulating angiogenic factors and endothelial activation/injury markers were serially assessed. The potential of CEPs to differentiate into mature endothelial cells was examined in cultures with angiogenic stimuli.Results. None of the patients experienced an adverse event, but 1 dropped out because of an excessive decrease in serum total cholesterol. Atorvastatin treatment resulted in a 1.7- to 8.0-fold increase in CEPs from baseline levels (P < 0.0001), but the numbers returned to within baseline levels at posttreatment. However, 8 patients (62%) experienced a gradual decrease in the number of CEPs, even while taking atorvastatin. Variables indicating the extent of Raynaud's phenomenon improved significantly, and up-regulated levels of angiogenic factors and vascular endothelial activation/injury markers decreased significantly during atorvastatin treatment. These variables returned to within baseline levels after discontinuation of the drug. In contrast, atorvastatin failed to improve the in vitro maturation potential of CEPs.Conclusion. The results of this pilot study suggest that atorvastatin treatment can increase CEPs and may be effective in improving Raynaud's phenomenon, even in SSc patients who have CEP dysfunction intrinsically.