TY - JOUR
T1 - Evidence for a derangement of the microvascular system in patients with a very early diagnosis of systemic sclerosis
AU - Chora, Inês
AU - Romano, Eloisa
AU - Manetti, Mirko
AU - Mazzotta, Celestina
AU - Costa, Raquel
AU - Machado, Vera
AU - Cortez, Alice
AU - Bruni, Cosimo
AU - Lepri, Gemma
AU - Guiducci, Serena
AU - De Paulis, Amato
AU - Soares, Raquel
AU - Matucci-Cerinic, Marco
N1 - Funding Information:
From the Department of Internal Medicine, São João Hospital Center, Al Prof Hernâni Monteiro; I3S, Instituto de Investigação e Inovação em Saúde, University of Porto; Departamento de Biomedicina, Unidade de Bioquímica, Faculty of Medicine, University of Porto; Nobre Laboratory, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Experimental and Clinical Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi (AOUC), University of Florence; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence; Department of Translational Medical Sciences, Centre for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy. IC was supported by a research grant from the Foundation for the Development of Internal Medicine in Europe. The study was partially funded by the Portuguese National Funding Agency (FCT: UID/BIM/04293/2013). I. Chora, MD, Department of Internal Medicine, São João Hospital Center, Al Prof Hernâni Monteiro, and I3S, University of Porto; E. Romano, PhD, Department of Experimental and Clinical Medicine, Division of Rheumatology, AOUC, University of Florence; M. Manetti, PhD, Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence; C. Mazzotta, PhD, Department of Experimental and Clinical Medicine, Division of Rheumatology, AOUC, University of Florence; R. Costa, MSc, I3S, University of Porto, and Departamento de Biomedicina, Unidade de Bioquímica, Faculty of Medicine, University of Porto; V. Machado, PhD, I3S, University of Porto, and Departamento de Biomedicina, Unidade de Bioquímica, Faculty of Medicine, University of Porto; A. Cortez, MSc, Nobre Laboratory, Faculty of Medicine, University of Porto; C. Bruni, MD, Department of Experimental and Clinical Medicine, Division of Rheumatology, AOUC, University of Florence; G. Lepri, MD, Department of Experimental and Clinical Medicine, Division of Rheumatology, AOUC, University of Florence; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Division of Rheumatology, AOUC, University of Florence; A. De Paulis, MD, Department of Translational Medical Sciences, CISI, University of Naples Federico II; R. Soares, PhD, I3S, University of Porto, and Departamento de Biomedicina, Unidade de Bioquímica, Faculty of Medicine, University of Porto; M. Matucci-Cerinic, MD, PhD, Department of Experimental and Clinical Medicine, Division of Rheumatology, AOUC, University of Florence. Address correspondence to Dr. I. Chora, Rua Faria de Guimarães, 649, 5º andar, 4200-291 Porto, Portugal. E-mail: [email protected] Accepted for publication April 11, 2017.
Publisher Copyright:
© The Journal of Rheumatology 2017.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Objective. To investigate whether patients with a very early diagnosis of systemic sclerosis (VEDOSS) may already present circulating markers and in vitro signs of microvascular dysfunction. Methods. Serum samples were obtained from 55 patients with systemic sclerosis (SSc), 25 patients with VEDOSS, and 55 matched healthy controls (HC). Serum levels of pan-vascular endothelial growth factor (VEGF) and soluble neuropilin-1 (sNRP-1) were measured by ELISA. Human dermal microvascular endothelial cells (H-MVEC) were cultured and stimulated with SSc, VEDOSS, and HC sera. Protein expression of NRP-1 was analyzed by Western blotting, cell proliferation by 5,-bromodeoxyuridine assay, migration capacity by wound-healing assay, and capillary-like tube formation by Matrigel assay. Results. Serum levels of pan-VEGF were increased in patients with VEDOSS and SSc versus HC (p = 0.05 and p = 0.003, respectively). Serum levels of sNRP-1 were significantly reduced in patients with VEDOSS and SSc compared with controls (p = 0.012 and p = 0.027, respectively). NRP-1 expression was decreased in H-MVEC stimulated with VEDOSS sera (p < 0.001 vs HC). Proliferation was reduced in H-MVEC stimulated either with VEDOSS or SSc sera in comparison with HC sera (p = 0.015 and p = 0.043, respectively). Wound healing was compromised in H-MVEC stimulated with VEDOSS and SSc sera versus HC sera (p < 0.01 for both). Capillarogenesis was decreased in H-MVEC stimulated with VEDOSS sera (p < 0.01) and SSc sera (p < 0.001) compared with cells stimulated with HC sera. Conclusion. Similar to patients with SSc, patients with VEDOSS already present biological signs of endothelial dysfunction. Our data demonstrate that VEDOSS sera significantly modify endothelial cell behavior and impair the angiogenic potential of the microvascular system.
AB - Objective. To investigate whether patients with a very early diagnosis of systemic sclerosis (VEDOSS) may already present circulating markers and in vitro signs of microvascular dysfunction. Methods. Serum samples were obtained from 55 patients with systemic sclerosis (SSc), 25 patients with VEDOSS, and 55 matched healthy controls (HC). Serum levels of pan-vascular endothelial growth factor (VEGF) and soluble neuropilin-1 (sNRP-1) were measured by ELISA. Human dermal microvascular endothelial cells (H-MVEC) were cultured and stimulated with SSc, VEDOSS, and HC sera. Protein expression of NRP-1 was analyzed by Western blotting, cell proliferation by 5,-bromodeoxyuridine assay, migration capacity by wound-healing assay, and capillary-like tube formation by Matrigel assay. Results. Serum levels of pan-VEGF were increased in patients with VEDOSS and SSc versus HC (p = 0.05 and p = 0.003, respectively). Serum levels of sNRP-1 were significantly reduced in patients with VEDOSS and SSc compared with controls (p = 0.012 and p = 0.027, respectively). NRP-1 expression was decreased in H-MVEC stimulated with VEDOSS sera (p < 0.001 vs HC). Proliferation was reduced in H-MVEC stimulated either with VEDOSS or SSc sera in comparison with HC sera (p = 0.015 and p = 0.043, respectively). Wound healing was compromised in H-MVEC stimulated with VEDOSS and SSc sera versus HC sera (p < 0.01 for both). Capillarogenesis was decreased in H-MVEC stimulated with VEDOSS sera (p < 0.01) and SSc sera (p < 0.001) compared with cells stimulated with HC sera. Conclusion. Similar to patients with SSc, patients with VEDOSS already present biological signs of endothelial dysfunction. Our data demonstrate that VEDOSS sera significantly modify endothelial cell behavior and impair the angiogenic potential of the microvascular system.
UR - http://www.scopus.com/inward/record.url?scp=85027866951&partnerID=8YFLogxK
U2 - 10.3899/jrheum.160791
DO - 10.3899/jrheum.160791
M3 - Article
C2 - 28507177
AN - SCOPUS:85027866951
SN - 0315-162X
VL - 44
SP - 1190
EP - 1197
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 8
ER -