Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension

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 a...

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Main Authors: Mattias Arvidsson, Abdulla Ahmed, Habib Bouzina, Göran Rådegran
Format: Article
Language:English
Published: SAGE Publishing 2019-12-01
Series:Pulmonary Circulation
Online Access:https://doi.org/10.1177/2045894019895414
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spelling doaj-a8ff2f2ef26e45a0a551a538abfa472e2020-11-25T03:44:47ZengSAGE PublishingPulmonary Circulation2045-89402019-12-01910.1177/2045894019895414Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertensionMattias Arvidsson0Abdulla Ahmed1Habib Bouzina2Göran Rådegran3The Hemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, SwedenThe Hemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, SwedenThe Hemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, SwedenThe Hemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, SwedenPulmonary 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.https://doi.org/10.1177/2045894019895414
collection DOAJ
language English
format Article
sources DOAJ
author Mattias Arvidsson
Abdulla Ahmed
Habib Bouzina
Göran Rådegran
spellingShingle Mattias Arvidsson
Abdulla Ahmed
Habib Bouzina
Göran Rådegran
Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
Pulmonary Circulation
author_facet Mattias Arvidsson
Abdulla Ahmed
Habib Bouzina
Göran Rådegran
author_sort Mattias Arvidsson
title Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
title_short Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
title_full Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
title_fullStr Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
title_full_unstemmed Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
title_sort matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
publisher SAGE Publishing
series Pulmonary Circulation
issn 2045-8940
publishDate 2019-12-01
description 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.
url https://doi.org/10.1177/2045894019895414
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