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- Arvidsson, Mattias, et al.
(författare)
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Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
- 2019
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Ingår i: Pulmonary Circulation. - : Wiley. - 2045-8932 .- 2045-8940. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary arterial hypertension is a severe disease for which diagnosis often is delayed. Matrix metalloproteinases have been suggested to play a role in vascular remodeling and pulmonary hypertension development. Our aim was therefore to investigate the potential role of matrix metalloproteinases as biomarkers in diagnosis and differentiation of pulmonary arterial hypertension in relation to various causes of dyspnea and pulmonary hypertension. Using proximity extension assays, 10 matrix metalloproteinases and associated proteins were analyzed in venous plasma from healthy controls (n = 20), as well as patients diagnosed with pulmonary arterial hypertension (n = 48), chronic thromboembolic pulmonary hypertension (n = 20), pulmonary hypertension due to heart failure with preserved (n = 33) or reduced (n = 36) ejection fraction, and heart failure with reduced ejection fraction and heart failure with preserved ejection fraction without pulmonary hypertension (n = 15). Plasma levels of matrix metalloproteinase-2, -7, -9, -12 and TIMP-4 were elevated (p < 0.01) in pulmonary arterial hypertension compared to controls. Plasma levels of matrix metalloproteinase-7 were furthermore lower (p < 0.0081) in pulmonary arterial hypertension than in all the other disease groups, but higher compared to controls (p < 0.0001). Receiver operating characteristic analysis of matrix metalloproteinase-7 resulted in sensitivity of 58.7% and a specificity of 83.3% for detecting pulmonary arterial hypertension among the other disease groups. Plasma matrix metalloproteinase-7 may provide a potential new diagnostic tool to differentiate pulmonary arterial hypertension from other causes of dyspnea, including heart failure with or without pulmonary hypertension and healthy controls. Matrix metalloproteinase-7 may furthermore be involved in the development of pulmonary hypertension and pulmonary arterial hypertension. Future studies investigating the clinical usefulness of matrix metalloproteinase-7 in the differentiation and earlier diagnosis of pulmonary arterial hypertension, as well as its relationship to pulmonary arterial hypertension pathogenesis, are encouraged.
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| 2. |
- Bouzina, Habib, et al.
(författare)
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Higher plasma fibroblast growth factor 23 levels are associated with a higher risk profile in pulmonary arterial hypertension
- 2019
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Ingår i: Pulmonary Circulation. - : Wiley. - 2045-8932 .- 2045-8940. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic abnormalities are proposed to contribute to pulmonary arterial as well as right ventricular remodelling in pulmonary arterial hypertension. Among the proposed abnormalities are altered glucose and lipid processing, mitochondrial malfunction, oxidative stress as well as vitamin D and iron abnormalities. In the present study, we investigated 11 metabolic plasma biomarkers, with the hypothesis that metabolic proteins may mirror disease severity in pulmonary arterial hypertension. Using proximity extension assays, plasma metabolic biomarkers were measured in 48 pulmonary arterial hypertension patients at diagnosis and, in 33 of them, at an early treatment follow-up, as well as in 16 healthy controls. Among the studied metabolic biomarkers, plasma fibroblast growth factor-23 (p < 0.001), fibroblast growth factor-21 (p < 0.001), fatty acid binding protein 4 (p < 0.001) and lectin-like oxidised low-density lipoprotein receptor 1 (p < 0.001) were increased and paraoxonase-3 was decreased (p < 0.001) in pulmonary arterial hypertension at diagnosis versus controls. Fibroblast growth factor-23 showed the strongest correlations to studied clinical parameters and was therefore selected for further analyses. Fibroblast growth factor-23 correlated specifically to mean right atrial pressure (r = 0.67, p < 0.001), six-min walking distance (r = −0.66, p < 0.001), NT-proBNP (r = 0.64, p < 0.001), venous oxygen saturation (r = −0.61, p < 0.001), cardiac index (r = −0.39, p < 0.007) and pulmonary vascular resistance (r = 0.37, p < 0.01). Fibroblast growth factor-23 correlated moreover to ESC/ERS (r = 0.72, p < 0.001) and the REVEAL risk score (r = 0.61, p < 0.001). Comparing early treatment follow-up with baseline, fibroblast growth factor-23 decreased (p < 0.02), with changes in fibroblast growth factor-23 correlating to changes in six-min walking distance (r = −0.56, p < 0.003), venous oxygen saturation (r = −0.46, p < 0.01), pulmonary vascular resistance (r = 0.43, p < 0.02), mean right atrial pressure (r = 0.38, p < 0.04) and cardiac index (r = −0.39, p < 0.04). Elevated plasma fibroblast growth factor-23 levels at pulmonary arterial hypertension diagnosis were associated with worse haemodynamics and a higher risk profile, and were decreased after the administration of pulmonary arterial hypertension-specific treatment.
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| 3. |
- Säleby, Joanna, et al.
(författare)
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Plasma receptor tyrosine kinase RET in pulmonary arterial hypertension diagnosis and differentiation
- 2019
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Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pulmonary arterial hypertension (PAH) is a serious disease exhibiting unspecific symptoms, as a result of which diagnosis is often delayed and prognosis is poor. The underlying pathophysiology includes vasoconstriction and remodelling of small pulmonary arteries. As receptor tyrosine kinases (RTKs) and their ligands have been shown to promote PAH remodelling, our aim was to evaluate if their plasma levels may be utilised to differentiate between various causes of pulmonary hypertension. Methods: 28 biomarkers involved in RTK signalling were measured using proximity extension assays in venous plasma from patients with PAH (n=48), chronic thromboembolic pulmonary hypertension (CTEPH) (n=20), pulmonary hypertension due to diastolic (n=33) or systolic (n=36) heart failure and heart failure patients without pulmonary hypertension (n=15), as well as healthy controls (n=20). Results: Plasma proto-oncogene tyrosine-protein kinase receptor Ret (RET) was decreased (p<0.04) in PAH compared with all disease groups and controls. RET generated a sensitivity of 64.6% and a specificity of 81.6% for detecting PAH from other disease groups. PAH and the other pulmonary hypertension groups showed elevated plasma tyrosine-protein kinase MER (p<0.01), vascular endothelial growth factor (VEGF)-A (p<0.02), VEGF-D (p<0.01), placental growth factor (p<0.01), amphiregulin (p<0.02), hepatocyte growth factor (p<0.01) and transforming growth factor-α (p<0.05) and decreased VEGF receptor-2 (p<0.04) and epidermal growth factor receptor (p<0.01) levels compared with controls. Conclusion: Plasma RET differentiates patients with PAH from those with CTEPH, systolic or diastolic heart failure with or without pulmonary hypertension as well as healthy controls. Future studies would be of value to determine the clinical usefulness of RET as a biomarker and its link to PAH pathophysiology.
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