Inês Chora1,2, Eloisa Romano3,4, Mirko Manetti3,4, Celestina Mazzotta3,4, Raquel Costa3,4, Vera Machado3,4, Alice Cortez3,4, Cosimo Bruni3,4, Gemma Lepri3,4, Serena Guiducci3,4, Amato De Paulis3,4, Raquel Soares3,4, Marco Matucci-Cerinic3,4. 1. 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. i_chora@yahoo.com. 2. 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. i_chora@yahoo.com. 3. 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. 4. 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.
Abstract
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.
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.
Entities:
Keywords:
ANGIOGENESIS; SYSTEMIC SCLEROSIS; VERY EARLY DIAGNOSIS OF SYSTEMIC SCLEROSIS
Authors: Amaal E Abdulle; Gilles F H Diercks; Martin Feelisch; Douwe J Mulder; Harry van Goor Journal: Front Physiol Date: 2018-08-24 Impact factor: 4.566
Authors: Lucio Díaz-Flores; Ricardo Gutiérrez; Maria Pino García; Miriam González-Gómez; Lucio Díaz-Flores; Jose Luis Carrasco; Juan Francisco Madrid; Aixa Rodríguez Bello Journal: Int J Mol Sci Date: 2022-08-12 Impact factor: 6.208