Title :

Biomarkers of haemodynamic severity of systemic sclerosis-associated pulmonary arterial hypertension by serum proteome analysis

Author(s) :

Sanges, Sébastien [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Rice, Lisa [Auteur]
Boston University School of Medicine [BUSM]
Tu, Ly [Auteur]
Centre Chirurgical Marie Lannelongue [CCML]
Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique [HPPIT]
Hypertension pulmonaire : physiopathologie et innovation thérapeutique [HPPIT]
Valenzi, Eleanor [Auteur]
University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] [UPMC]
Cracowski, Jean-Luc [Auteur]
Hypoxie et PhysioPathologie [HP2]
Centre Hospitalier Universitaire [CHU Grenoble] [CHUGA]
Montani, David [Auteur]
Hypertension pulmonaire : physiopathologie et innovation thérapeutique [HPPIT]
Mantero, Julio [Auteur]
Boston University School of Medicine [BUSM]
Ternynck, Camille [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Marot, Guillemette [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
MOdel for Data Analysis and Learning [MODAL]
Bujor, Andreea [Auteur]
Boston University School of Medicine [BUSM]
Hachulla, Eric [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Launay, David [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Humbert, Marc [Auteur]
Hypertension pulmonaire : physiopathologie et innovation thérapeutique [HPPIT]
Centre de Référence de l’Hypertension Pulmonaire Sévère [CHU Le Kremlin Bicêtre]
Guignabert, Christophe [Auteur]
Hypertension pulmonaire : physiopathologie et innovation thérapeutique [HPPIT]
Lafyatis, Robert [Auteur]
University of Pittsburgh School of Medicine

Journal title :

Annals of the Rheumatic Diseases

Pages :

365-373

Publisher :

BMJ Publishing Group

Publication date :

2023-03-05

ISSN :

0003-4967

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Objectives To mine the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and to detect biomarkers that may assist in earlier and more effective diagnosis and treatment. ...
Show more >Objectives To mine the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and to detect biomarkers that may assist in earlier and more effective diagnosis and treatment. Methods Patients with limited cutaneous SSc, no extensive interstitial lung disease and no PAH-specific therapy were included. They were classified as cases if they had PAH confirmed by right heart catheterisation (RHC) and serum collected on the same day as RHC; and as controls if they had no clinical evidence of PAH. Results Patients were mostly middle-aged females with anticentromere-associated SSc. Among 1129 proteins assessed by a high-throughput proteomic assay (SOMAscan), only 2 were differentially expressed and correlated significantly with pulmonary vascular resistance (PVR) in SSc-PAH patients (n=15): chemerin ( ρ =0.62, p=0.01) and SET ( ρ =0.62, p=0.01). To validate these results, serum levels of chemerin were measured by ELISA in an independent cohort. Chemerin levels were confirmed to be significantly higher (p=0.01) and correlate with PVR ( ρ =0.42, p=0.04) in SSc-PAH patients (n=24). Chemerin mRNA expression was detected in fibroblasts, pulmonary artery smooth muscle cells (PA-SMCs)/pericytes and mesothelial cells in SSc-PAH lungs by single-cell RNA-sequencing. Confocal immunofluorescence revealed increased expression of a chemerin receptor, CMKLR1, on SSc-PAH PA-SMCs. SSc-PAH serum seemed to induce higher PA-SMC proliferation than serum from SSc patients without PAH. This difference appeared neutralised when adding the CMKLR1 inhibitor α-NETA. Conclusion Chemerin seems an interesting surrogate biomarker for PVR in SSc-PAH. Increased chemerin serum levels and CMKLR1 expression by PA-SMCs may contribute to SSc-PAH pathogenesis by inducing PA-SMC proliferation.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Laboratoire Paul Painlevé - UMR 8524

Source :

Harvested from HAL