Longterm Effects of Endothelin Receptor Antagonism on Microvascular Damage Evaluated by Nailfold Capillaroscopic Analysis in Systemic Sclerosis
Longterm Effects of Endothelin Receptor Antagonism on Microvascular Damage Evaluated by Nailfold Capillaroscopic Analysis in Systemic Sclerosis
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DOI：
10.3899/jrheum.120416
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发表时间：
2013-01-01
影响因子：
3.9
通讯作者：
Sulli, Alberto
中科院分区：
文献类型：
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作者：
Cutolo, Maurizio;Zampogna, Giuseppe;Sulli, Alberto
Objective.系统性硬化症（SSc）的特征是微血管损伤、纤维化和相关组织的缺氧。血管活性肽内皮素-1（ET-1）似乎与这些事件有关。使用甲襞视频毛细血管镜检查（NYC），我们评估了3年随访期内ET-1拮抗剂治疗对SSc患者甲襞微血管损伤的长期影响。30例SSc患者（平均年龄64 +/- 5岁，平均病程8 +/- 1年）在其程序化标准治疗方案期间招募。在基线（TO）时，15例SSc患者（平均年龄63 ± 15岁，平均病程7 ± 3年）已接受伊洛前列素循环静脉输注（连续5天，平均80 μ g/天，每3个月一次），继续治疗3年（ILO组）。其余15例SSc患者（平均年龄68 ± 13岁，平均病程8 ± 4年）虽然继续接受与前一组相同的伊洛前列素周期性静脉给药治疗，但也接受波生坦125 mg每日两次治疗3年（ILO+BOS组）。采用经验证的常规NYC方法进行定性分析（硬皮病模式）和微血管损伤的半定量评分。随访期间，ILO+BOS组毛细血管数量显著增加（p < 0.02），血管生成显著增加（p < 0.01）。相比之下，ILO组显示出统计学上显著的毛细血管数目减少（p < 0.05）。3年后，ILO+BOS组毛细血管数量明显高于ILO组（p < 0.05）。两组患者的巨毛细血管评分均显著降低（p < 0.05）。在这项开放性研究中，发现ET-1受体拮抗剂联合伊洛前列素长期治疗可干扰SSc患者甲襞微血管损伤的进展，由NYC在3年随访期内进行评估。（2012年11月1日首次发布; J Rheumol 2013;40：40-5; doi：10.3899/jrheum.120416）
Objective. Systemic sclerosis (SSc) is characterized by microvascular injury, fibrosis, and hypoxia of involved tissues. The vasoactive peptide endothelin-1 (ET-1) seems to be implicated in these events. Using nailfold videocapillaroscopy (NYC), we evaluated longterm effects of ET-1 antagonist treatment on nailfold microvascular damage in patients with SSc, over a 3-year followup period.Methods. Thirty patients with SSc (mean age 64 +/- 5 yrs, mean disease duration 8 +/- 1 yrs) were recruited during their programmed standard treatment protocols. At baseline (TO), 15 patients with SSc (mean age 63 +/- 15 yrs, mean disease duration 7 +/- 3 yrs), already receiving cyclic intravenous infusion of iloprost (5 continuous days, average 80 mu g/day, every 3 mo), continued the treatment for a further 3 years (ILO group). The remaining 15 patients with SSc (mean age 68 +/- 13 yrs, mean disease duration 8 +/- 4 yrs), although they continued the same cyclic intravenous iloprost treatment as the previous group, also received bosentan 125 mg twice a day for 3 years (ILO+BOS group). Qualitative analysis (scleroderma patterns) and semiquantitative scoring of the microvascular damage were performed by validated routine NYC methods.Results. During followup, a statistically significant increase of capillary number was observed in the ILO+BOS group (p < 0.02), with a significant and progressive increase of angiogenesis (p < 0.01). In contrast, the ILO group showed a statistically significant decrease of capillary number (p < 0.05). After 3 years the number of capillaries was significantly higher in the ILO+BOS group than in the ILO group (p < 0.05). The score for giant capillaries decreased significantly in both groups of patients with SSc (p < 0.05).Conclusion. In this open study, longterm treatment with ET-1 receptor antagonist in combination with iloprost was found to interfere with progression of nailfold microvascular damage in patients with SSc, as assessed by NYC over a 3-year followup period. (First Release Nov 1 2012; J Rheumatol 2013;40:40-5; doi:10.3899/jrheum.120416)