Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic Sclerosis
<b>Introduction:</b> Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are severe complications of patients with systemic sclerosis (SSc). Currently, there are a few tests for early identification of these conditions, although they are invasive and time-consuming....
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2025-02-01
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| author | Stelvio Tonello Davide D’Onghia Annalisa Di Ruscio Silvia Maria Mora Federica Vincenzi Giulia Caria Alessia Fracchia Nicole Vercellino Benedetta Bussolati Adele Tanzi Manuela Rizzi Rosalba Minisini Daniele Sola Massimo Scacchi Stefania Mai Mario Pirisi Carlo Smirne Elena Grossini Vincenzo Cantaluppi Cristoforo Comi Giuseppe Murdaca Donato Colangelo Pier Paolo Sainaghi |
| author_facet | Stelvio Tonello Davide D’Onghia Annalisa Di Ruscio Silvia Maria Mora Federica Vincenzi Giulia Caria Alessia Fracchia Nicole Vercellino Benedetta Bussolati Adele Tanzi Manuela Rizzi Rosalba Minisini Daniele Sola Massimo Scacchi Stefania Mai Mario Pirisi Carlo Smirne Elena Grossini Vincenzo Cantaluppi Cristoforo Comi Giuseppe Murdaca Donato Colangelo Pier Paolo Sainaghi |
| author_sort | Stelvio Tonello |
| collection | DOAJ |
| description | <b>Introduction:</b> Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are severe complications of patients with systemic sclerosis (SSc). Currently, there are a few tests for early identification of these conditions, although they are invasive and time-consuming. Extracellular vesicles (EVs) offer a promising possibility for gathering information on tissue health. This study aims to characterize EVs in cases of systemic sclerosis complicated by pulmonary hypertension and pulmonary fibrosis. <b>Methods:</b> A cohort of 58 patients with SSc was evaluated, including 14 with pulmonary hypertension, 17 with pulmonary fibrosis, and 27 without complications. Additionally, 11 healthy subjects, matched for sex and age, served as a control group. EVs were characterized by using a MACSplex kit to analyze the expression of 37 membrane markers. <b>Results:</b> After the overall analysis, we show that EVs from SSc patients had higher expression of CD146, CD42a, and CD29 (<i>p</i> = 0.03, <i>p</i> = 0.02 and <i>p</i> = 0.05) but lower expression of HLA-ABC with respect to the control patients (<i>p</i> = 0.02). Multivariate analyses demonstrated that only CD42a has a significant association with the disease (<i>p</i> = 0.0478). In group comparative analyses (PAH, ILD, uncomplicated systemic sclerosis (named SSc no PAH no ILD), and controls), CD3 and CD56 were higher in PAH patients, with respect to the controls, ILD, and the group SSc no PAH no ILD (CD3: <i>p</i> = 0.01, <i>p</i> = 0.003, <i>p</i> = 0.0005; CD56: <i>p</i> = 0.002, <i>p</i> < 0.0001, <i>p</i> = 0.0002). HLA-DR showed higher expression in PAH patients with respect to ILD patients (<i>p</i> = 0.02), CD25 showed higher expression in PAH patients with respect uncomplicated SSc (<i>p</i> = 0.02), and CD42a showed higher expression in PAH patients with respect to the controls (<i>p</i> = 0.03); nevertheless, multivariate analyses demonstrated that only CD3 retained its association with PAH. <b>Conclusions:</b> The expression of CD42a, a platelet-derived marker indicating endothelial damage, suggests its potential to provide information on the state of the microcirculation in systemic sclerosis. The higher expression of CD3 on the surface of the EVs in PAH patients might indicate increased T-cell activity in tissues, with a possible association with the development of pulmonary hypertension. |
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| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-9e14b1bd9c2041c4a6c21f56c3686f6d2025-08-20T03:12:12ZengMDPI AGPharmaceuticals1424-82472025-02-0118225910.3390/ph18020259Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic SclerosisStelvio Tonello0Davide D’Onghia1Annalisa Di Ruscio2Silvia Maria Mora3Federica Vincenzi4Giulia Caria5Alessia Fracchia6Nicole Vercellino7Benedetta Bussolati8Adele Tanzi9Manuela Rizzi10Rosalba Minisini11Daniele Sola12Massimo Scacchi13Stefania Mai14Mario Pirisi15Carlo Smirne16Elena Grossini17Vincenzo Cantaluppi18Cristoforo Comi19Giuseppe Murdaca20Donato Colangelo21Pier Paolo Sainaghi22Department on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyCancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA 02215, USADepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyMolecular Biotechnology Center “Guido Tarone”, Department of Molecular Biotechnology and Health Sciences, Università di Torino, 10125 Torino, ItalyMolecular Biotechnology Center “Guido Tarone”, Department of Molecular Biotechnology and Health Sciences, Università di Torino, 10125 Torino, ItalyHuman Anatomy Laboratory, Department of Health Sciences, Università del Piemonte Orientale (UPO), 28100 Novara, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyLaboratory of Metabolic Research, IRCCS Istituto Auxologico Italiano, 28824 Oggebbio, ItalyLaboratory of Metabolic Research, IRCCS Istituto Auxologico Italiano, 28824 Oggebbio, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyLaboratory of Physiology, Department of Translational Medicine, Università del Piemonte Orientale (UPO), 28100 Novara, ItalyNephrology Unit, Department of Translational Medicine, Università del Piemonte Orientale (UPO), 28100 Novara, ItalyNeurology Unit, Department of Translational Medicine, Università del Piemonte Orientale (UPO), 28100 Novara, ItalyDepartment of Internal Medicine, University of Genova, 16132 Genova, ItalyPharmacology, Department of Health Sciences, Università del Piemonte Orientale (UPO), 28100 Novara, ItalyDepartment on Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy<b>Introduction:</b> Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are severe complications of patients with systemic sclerosis (SSc). Currently, there are a few tests for early identification of these conditions, although they are invasive and time-consuming. Extracellular vesicles (EVs) offer a promising possibility for gathering information on tissue health. This study aims to characterize EVs in cases of systemic sclerosis complicated by pulmonary hypertension and pulmonary fibrosis. <b>Methods:</b> A cohort of 58 patients with SSc was evaluated, including 14 with pulmonary hypertension, 17 with pulmonary fibrosis, and 27 without complications. Additionally, 11 healthy subjects, matched for sex and age, served as a control group. EVs were characterized by using a MACSplex kit to analyze the expression of 37 membrane markers. <b>Results:</b> After the overall analysis, we show that EVs from SSc patients had higher expression of CD146, CD42a, and CD29 (<i>p</i> = 0.03, <i>p</i> = 0.02 and <i>p</i> = 0.05) but lower expression of HLA-ABC with respect to the control patients (<i>p</i> = 0.02). Multivariate analyses demonstrated that only CD42a has a significant association with the disease (<i>p</i> = 0.0478). In group comparative analyses (PAH, ILD, uncomplicated systemic sclerosis (named SSc no PAH no ILD), and controls), CD3 and CD56 were higher in PAH patients, with respect to the controls, ILD, and the group SSc no PAH no ILD (CD3: <i>p</i> = 0.01, <i>p</i> = 0.003, <i>p</i> = 0.0005; CD56: <i>p</i> = 0.002, <i>p</i> < 0.0001, <i>p</i> = 0.0002). HLA-DR showed higher expression in PAH patients with respect to ILD patients (<i>p</i> = 0.02), CD25 showed higher expression in PAH patients with respect uncomplicated SSc (<i>p</i> = 0.02), and CD42a showed higher expression in PAH patients with respect to the controls (<i>p</i> = 0.03); nevertheless, multivariate analyses demonstrated that only CD3 retained its association with PAH. <b>Conclusions:</b> The expression of CD42a, a platelet-derived marker indicating endothelial damage, suggests its potential to provide information on the state of the microcirculation in systemic sclerosis. The higher expression of CD3 on the surface of the EVs in PAH patients might indicate increased T-cell activity in tissues, with a possible association with the development of pulmonary hypertension.https://www.mdpi.com/1424-8247/18/2/259extracellular vesiclessystemic sclerosispulmonary hypertensionpulmonary fibrosisautoimmunity |
| spellingShingle | Stelvio Tonello Davide D’Onghia Annalisa Di Ruscio Silvia Maria Mora Federica Vincenzi Giulia Caria Alessia Fracchia Nicole Vercellino Benedetta Bussolati Adele Tanzi Manuela Rizzi Rosalba Minisini Daniele Sola Massimo Scacchi Stefania Mai Mario Pirisi Carlo Smirne Elena Grossini Vincenzo Cantaluppi Cristoforo Comi Giuseppe Murdaca Donato Colangelo Pier Paolo Sainaghi Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic Sclerosis Pharmaceuticals extracellular vesicles systemic sclerosis pulmonary hypertension pulmonary fibrosis autoimmunity |
| title | Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic Sclerosis |
| title_full | Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic Sclerosis |
| title_fullStr | Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic Sclerosis |
| title_full_unstemmed | Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic Sclerosis |
| title_short | Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic Sclerosis |
| title_sort | extracellular vesicles as a potential biomarker of pulmonary arterial hypertension in systemic sclerosis |
| topic | extracellular vesicles systemic sclerosis pulmonary hypertension pulmonary fibrosis autoimmunity |
| url | https://www.mdpi.com/1424-8247/18/2/259 |
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