Dephosphorylated uncarboxylated Matrix-Gla-Protein as candidate biomarker for immune-mediated vascular remodeling and prognosis in pulmonary hypertension

Dephosphorylated uncarboxylated Matrix-Gla-Protein as candidate biomarker for immune-mediated vascular remodeling and prognosis in pulmonary hypertension

Abstract Pulmonary arterial hypertension (PAH) is a disease characterized by pulmonary vascular remodeling. Since dephosphorylated-uncarboxylated Matrix Gla-Protein (dp-ucMGP) is associated with cardiovascular mortality in systemic sclerosis, a disease associated with PAH, and immune-system involvem...

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Main Authors: R. Tobal, J. Potjewijd, F. de Vries, D. P.C. van Doorn, A. Jaminon, R. Bittner, C. Akbulut, V. van Empel, P. Heeringa, J. Damoiseaux, L. Schurgers, P. van Paassen
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
Subjects:
Pulmonary hypertension
Vascular remodeling
Dp-ucMGP
Inflammation
Immune checkpoint proteins
Biomarkers
Online Access:https://doi.org/10.1038/s41598-024-77000-w
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Summary:Abstract Pulmonary arterial hypertension (PAH) is a disease characterized by pulmonary vascular remodeling. Since dephosphorylated-uncarboxylated Matrix Gla-Protein (dp-ucMGP) is associated with cardiovascular mortality in systemic sclerosis, a disease associated with PAH, and immune-system involvement in PAH is increasingly recognized, we investigated the relationship between dp-ucMGP, vascular remodeling and soluble immune-checkpoint proteins in PAH. This prospective cohort study included patients with idiopathic (I)PAH, connective tissue disease (CTD)-PAH, chronic thrombo-embolic PH (CTEPH) and CTD patients without PAH. Patients with IPAH and CTD-PAH were stratified by clinical signs of immune-mediated inflammatory disease (IMID). We measured dp-ucMGP plasma levels, soluble immune-checkpoint proteins (sICPs), and vascular smooth muscle cell (iVSMC) calcification. We found elevated dp-ucMGP levels in all PAH subtypes and CTD patients compared to healthy controls. PAH patients showed increased iVSMC calcification, but no direct correlation was found with dp-ucMGP. IMID-PAH patients had higher dp-ucMGP levels than non-IMID PAH patients. dp-ucMGP correlated with several sICPs in both IPAH and CTD patients; multiple sICPs were elevated in IMID PAH patients. High dp-ucMGP levels in IPAH patients were associated with worse survival. Our findings suggest dp-ucMGP as a potential biomarker of immune-mediated vascular remodeling in PAH. Hence, dp-ucMGP, could help identify PAH patients who might benefit from immunosuppressive therapies.
ISSN:2045-2322

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