title: Impaired angiogenesis as a feature of digital ulcers in systemic sclerosis.
abstract: 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.
authors.affiliation: Angiology and Vascular Surgery Service and Clinical Immunology Unit, Centro Hospitalar do Porto, Porto, Portugal. heitor.ivone@gmail.com.
authors.forename: Ivone
authors.initials: I
authors.lastname: Silva
authors.affiliation: Internal Medicine, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Almeida
authors.affiliation: Health Information and Decision Sciences Department, CINTESIS- Center for Research in Health Technologies and Information Systems, Universidade do Porto, Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Teixeira
authors.affiliation: Clinical Pathology Department, Clinical Chemistry, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: Clinical Immunology Unit, Centro Hospitalar do Porto; Instituto de Ciências Biomédicas Abel Salazar, Multidisciplinar Unit of biomedical investigation, University of Porto, Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vasconcelos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D000071063:Endoglin / Q000097:blood*; D043169:Endostatins / Q000097:blood*; D005260:Female; D005385:Fingers / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D020678:Microscopic Angioscopy; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic; D011174:Portugal; D011446:Prospective Studies; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000097:blood* / Q000150:complications; D012883:Skin Ulcer / Q000097:blood / Q000175:diagnosis*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; D043169:Endostatins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Capillaroscopy; Digital ulcers; Endoglin; Endostatin; Systemic sclerosis; VEGF