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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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-77000-w |
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| author | 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 |
| author_facet | 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 |
| author_sort | R. Tobal |
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| description | 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. |
| format | Article |
| id | doaj-art-f818e9226fb64d1db9cbb3786ceb7172 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-f818e9226fb64d1db9cbb3786ceb71722024-11-10T12:19:12ZengNature PortfolioScientific Reports2045-23222024-11-0114111210.1038/s41598-024-77000-wDephosphorylated uncarboxylated Matrix-Gla-Protein as candidate biomarker for immune-mediated vascular remodeling and prognosis in pulmonary hypertensionR. Tobal0J. Potjewijd1F. de Vries2D. P.C. van Doorn3A. Jaminon4R. Bittner5C. Akbulut6V. van Empel7P. Heeringa8J. Damoiseaux9L. Schurgers10P. van Paassen11Department of Internal Medicine, Division of Clinical and Experimental Immunology, Maastricht University Medical CenterDepartment of Internal Medicine, Division of Clinical and Experimental Immunology, Maastricht University Medical CenterDepartment of Biochemistry, CARIM, Maastricht UniversityDepartment of Internal Medicine, Division of Clinical and Experimental Immunology, Maastricht University Medical CenterDepartment of Biochemistry, CARIM, Maastricht UniversityDepartment of Biochemistry, CARIM, Maastricht UniversityDepartment of Biochemistry, CARIM, Maastricht UniversityDepartment of Cardiology, Maastricht University Medical CenterDepartment of Pathology and Medical Biology, University Medical Center GroningenCentral Diagnostic Laboratory, Maastricht University Medical CenterDepartment of Biochemistry, CARIM, Maastricht UniversityDepartment of Internal Medicine, Division of Clinical and Experimental Immunology, Maastricht University Medical CenterAbstract 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.https://doi.org/10.1038/s41598-024-77000-wPulmonary hypertensionVascular remodelingDp-ucMGPInflammationImmune checkpoint proteinsBiomarkers |
| spellingShingle | 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 Dephosphorylated uncarboxylated Matrix-Gla-Protein as candidate biomarker for immune-mediated vascular remodeling and prognosis in pulmonary hypertension Scientific Reports Pulmonary hypertension Vascular remodeling Dp-ucMGP Inflammation Immune checkpoint proteins Biomarkers |
| title | Dephosphorylated uncarboxylated Matrix-Gla-Protein as candidate biomarker for immune-mediated vascular remodeling and prognosis in pulmonary hypertension |
| title_full | Dephosphorylated uncarboxylated Matrix-Gla-Protein as candidate biomarker for immune-mediated vascular remodeling and prognosis in pulmonary hypertension |
| title_fullStr | Dephosphorylated uncarboxylated Matrix-Gla-Protein as candidate biomarker for immune-mediated vascular remodeling and prognosis in pulmonary hypertension |
| title_full_unstemmed | Dephosphorylated uncarboxylated Matrix-Gla-Protein as candidate biomarker for immune-mediated vascular remodeling and prognosis in pulmonary hypertension |
| title_short | Dephosphorylated uncarboxylated Matrix-Gla-Protein as candidate biomarker for immune-mediated vascular remodeling and prognosis in pulmonary hypertension |
| title_sort | dephosphorylated uncarboxylated matrix gla protein as candidate biomarker for immune mediated vascular remodeling and prognosis in pulmonary hypertension |
| topic | Pulmonary hypertension Vascular remodeling Dp-ucMGP Inflammation Immune checkpoint proteins Biomarkers |
| url | https://doi.org/10.1038/s41598-024-77000-w |
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