Academic Journal
Transpulmonary proteomic gradient analysis in women with pulmonary arterial hypertension associated with systemic sclerosis.
| Τίτλος: | Transpulmonary proteomic gradient analysis in women with pulmonary arterial hypertension associated with systemic sclerosis. |
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| Συγγραφείς: | Teixeira M; Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal. Electronic address: manuelteixeira@ua.pt., Couto DS; Department of Cardiology, Pulmonary Vascular Disease Unit, Unidade Local de Saúde de Santo António, Porto, Portugal; Department of Immuno-Physiology and Pharmacology, Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal., Oliveira MI; Department of Immuno-Physiology and Pharmacology, Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal; Physical Activity, Health and Leisure Research Centre (CIAFEL), Faculty of Sports, University of Porto, Porto, Portugal., Aires I; Mass Spectrometry Centre, LAQV-REQUIMTE - Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology, Department of Chemistry, University of Aveiro, Aveiro, Portugal., Domingues P; Mass Spectrometry Centre, LAQV-REQUIMTE - Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology, Department of Chemistry, University of Aveiro, Aveiro, Portugal., Ribeiro F; Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal., Santos M; Department of Cardiology, Pulmonary Vascular Disease Unit, Unidade Local de Saúde de Santo António, Porto, Portugal; Department of Immuno-Physiology and Pharmacology, Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal; ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal. Electronic address: mariossantos001@gmail.com. |
| Πηγή: | Journal of proteomics [J Proteomics] 2026 Oct 15; Vol. 331, pp. 105703. Date of Electronic Publication: 2026 Jun 30. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101475056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1876-7737 (Electronic) Linking ISSN: 18743919 NLM ISO Abbreviation: J Proteomics Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier |
| Ιατρικοί όροι (MeSH): | Scleroderma, Systemic*/complications , Scleroderma, Systemic*/metabolism , Proteomics*/methods , Proteome*/metabolism , Proteome*/analysis , Hypertension, Pulmonary*/metabolism , Pulmonary Arterial Hypertension*/metabolism, Pulmonary Artery/metabolism ; Humans ; Female ; Middle Aged ; Aged ; Biomarkers |
| Περίληψη: | This study investigated proteomic alterations in the pulmonary circulation of patients with pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) by analyzing the transpulmonary protein gradient and comparing the proteomic profiles with systemic sclerosis (SSc) without PAH. Twenty women were included (10 PAH-SSc, 64.6 ± 10.8 years; 10 SSc, 62.8 ± 11.5 years). The transpulmonary gradient was defined as the difference in biomarker concentrations between wedge-position and pulmonary artery blood samples. Peptides were analysed using liquid chromatography-mass spectrometry, and differentially abundant proteins were identified with Proteome Discoverer. Protein-protein interaction networks were generated with STRING and visualized in Cytoscape. A total of 270 proteins were detected, with no significant transpulmonary gradient alterations. However, patients with PAH-SSc showed distinct proteomic profiles compared to SSc. Multivariate analysis identified 48 differentially abundant proteins in pulmonary artery plasma, with 15 overrepresented and 33 downregulated in PAH-SSc. Among these, the downregulation of transforming growth factor-beta-induced protein ig-h3 (TGFβI/ig-h3) points to a potential involvement of the TGF-β-related extracellular matrix remodelling pathway in PAH-SSc. However, further validation in larger and independent cohorts is required before its relevance as a biomarker or therapeutic target can be established. In conclusion, while no transpulmonary proteomic gradient was observed, the proteomic profiles of PAH-SSc and SSc were different. The profile in PAH-SSc was characterized by differences in immune response, lipid metabolism, and hemostatic proteins. SIGNIFICANCE: This study offers the first proteomic characterization of the transpulmonary gradient in PAH-SSc and SSc. Although no differences in the gradient were found, the pulmonary artery plasma proteome of PAH-SSc patients showed a distinct pattern compared to SSc. Several proteins associated with immune function, haemostasis, and cellular processes were altered, which may indicate specific pathophysiological features of PAH-SSc or suggest how lung dysfunction develops in SSc. Targeting dysregulated proteins like TGFβI/ig-h3 or addressing immune-coagulation imbalances may support future research studies. Overall, these findings refine the molecular profile of PAH-SSc and provide a basis for future large-scale studies aimed at clarifying disease mechanisms and identifying clinically relevant molecular signatures. (Copyright © 2026. Published by Elsevier B.V.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no conflict of interest. |
| Contributed Indexing: | Keywords: Mass spectrometry; Proteomics; Pulmonary hypertension; Systemic sclerosis; Transpulmonary gradient |
| Substance Nomenclature: | 0 (Proteome) 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260630 Date Completed: 20260902 Latest Revision: 20260902 |
| Update Code: | 20260903 |
| DOI: | 10.1016/j.jprot.2026.105703 |
| PMID: | 42379418 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1876-7737 |
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| DOI: | 10.1016/j.jprot.2026.105703 |