Silva Ivone, Almeida Cristiana, Teixeira Andreia, Oliveira José, Vasconcelos Carlos
Angiology and Vascular Surgery Service and Clinical Immunology Unit, Centro Hospitalar do Porto, Porto, Portugal.
Internal Medicine, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.
Clin Rheumatol. 2016 Jul;35(7):1743-51. doi: 10.1007/s10067-016-3219-8. Epub 2016 Feb 26.
Impaired angiogenesis in systemic sclerosis has a major role in tissue injury pathogenesis. Our objective was to determine whether angiogenic biomarkers (vascular endothelial growth factor (VEGF), endoglin, and endostatin) are related to microvascular damage and to determine their predictive value for new digital ulcers (DU). The main outcome of the study was the occurrence of a new digital ulcer during 3-year follow-up. This prospective longitudinal study was performed between October 2011 and December 2014. Seventy-seven patients definitely diagnosed with systemic sclerosis where divided into two groups: those with active DU at baseline and those with no DU until enrollment. Patients were matched by sex and age with healthy controls. Serum levels of VEGF, endoglin, and endostatin were measured at enrollment, and several nailfold videocapillaroscopies were performed during the 3-year follow-up. Serum levels of VEGF were lower (245.06, 158.68-347.33; p < 0.001) and those of endoglin were higher (3.013, 1.463-7.023; p < 0.001) in patients with active DU than those with no DU history (339.49, 202.00-730.93/1.879, 0.840-3.280), and they were higher than those found in controls (178.030, 101.267-222.102)/0.277, 0.154-0.713), respectively. No differences in endostatin levels were found between groups (p = 0.450). Endoglin was the only biomarker significantly different (p = 0.031) between patients with diffuse versus limited systemic sclerosis and between early, active, and late patterns (p = 0.020). VEGF was identified as an independent predictor for the development of new DU. Our study confirmed the relationship between angiogenic vascular biomarkers and the occurrence of DU. Endoglin and VEGF serum levels are potential risk factors, and VEGF has a predictive value for the occurrence of new DU.
系统性硬化症中血管生成受损在组织损伤发病机制中起主要作用。我们的目的是确定血管生成生物标志物（血管内皮生长因子（VEGF）、内皮糖蛋白和内皮抑素）是否与微血管损伤相关，并确定它们对新发指端溃疡（DU）的预测价值。该研究的主要结局是在3年随访期间出现新发指端溃疡。这项前瞻性纵向研究于2011年10月至2014年12月进行。77例确诊为系统性硬化症的患者被分为两组：基线时有活动性DU的患者和入组前无DU的患者。患者按性别和年龄与健康对照进行匹配。在入组时测量VEGF、内皮糖蛋白和内皮抑素的血清水平，并在3年随访期间进行多次甲襞微血管显微镜检查。与无DU病史的患者（339.49，202.00 - 730.93/1.879，0.840 - 3.280）相比，活动性DU患者的VEGF血清水平较低（245.06，158.68 - 347.33；p＜0.001），内皮糖蛋白水平较高（3.013，1.463 - 7.023；p＜0.001），且分别高于对照组（178.030，101.267 - 222.102/0.277，0.154 - 0.713）。两组间内皮抑素水平无差异（p = 0.450）。内皮糖蛋白是弥漫性与局限性系统性硬化症患者之间以及早期、活动期和晚期模式之间唯一有显著差异的生物标志物（p = 0.031）（p = 0.020）。VEGF被确定为新发DU发生的独立预测因子。我们的研究证实了血管生成血管生物标志物与DU发生之间的关系。内皮糖蛋白和VEGF血清水平是潜在危险因素，且VEGF对新发DU的发生具有预测价值。
