Impaired angiogenesis as a feature of digital ulcers in systemic sclerosis

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.