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Plasma matrix metalloproteinase 2 is associated with severity and mortality in pulmonary arterial hypertension

Arvidsson, Mattias LU orcid ; Ahmed, Abdulla LU orcid ; Säleby, Joanna LU ; Hesselstrand, Roger LU and Rådegran, Göran LU (2022) In Pulmonary Circulation 12(1).
Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by vasoconstriction and remodeling of the pulmonary vessels. Risk stratification in PAH could potentially be improved by including novel biomarkers related to PAH pathobiology. We aimed to investigate the relationship between extracellular matrix (ECM)-related proteins, survival, and European Society of Cardiology and European Respiratory Society (ESC/ERS) risk stratification scores in patients with PAH. Plasma samples and hemodynamics were collected from PAH patients during right heart catheterizations at diagnosis (n = 48) and early follow-up, after treatment initiation (n = 33). Plasma levels of 14 ECM-related proteins, with altered levels in PAH... (More)

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by vasoconstriction and remodeling of the pulmonary vessels. Risk stratification in PAH could potentially be improved by including novel biomarkers related to PAH pathobiology. We aimed to investigate the relationship between extracellular matrix (ECM)-related proteins, survival, and European Society of Cardiology and European Respiratory Society (ESC/ERS) risk stratification scores in patients with PAH. Plasma samples and hemodynamics were collected from PAH patients during right heart catheterizations at diagnosis (n = 48) and early follow-up, after treatment initiation (n = 33). Plasma levels of 14 ECM-related proteins, with altered levels in PAH compared to healthy controls, were analyzed with proximity extension assays, and related to hemodynamics, transplant-free survival time, and ESC/ERS risk score. Glypican-1 levels were higher before versus after treatment initiation (p = 0.048). PAH patients with high plasma levels of matrix metalloproteinase (MMP) -2, MMP-7, MMP-9, MMP-12, perlecan, and tissue inhibitor of metalloproteinase 4 (TIMP-4) at baseline, had worse transplant-free survival (p < 0.03) than patients with low levels. Hazard ratio (95% confidence interval) was for MMP-2 1.126 (1.011–1.255), perlecan 1.0099 (1.0004–1.0196), and TIMP-4 1.037 (1.003–1.071) in age and sex-adjusted Cox-regression model. MMP-2 correlated with ESC/ERS risk scores (rs = 0.34, p = 0.019), mean right atrial pressure (rs = 0.44, p = 0.002), NT-proBNP (rs = 0.49, p ≤ 0.001), and six-minute walking distance (rs = −0.34, p = 0.02). The present study indicates that high levels of MMP-2, perlecan, and TIMP-4 are associated with poor survival in PAH. High plasma MMP-2, correlated with poor prognosis in PAH. Further validation in larger studies is needed to better determine this association.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
extracellular matrix, matrix metalloproteinase-2, prognosis, pulmonary arterial hypertension, risk assessment
in
Pulmonary Circulation
volume
12
issue
1
article number
e12041
publisher
SAGE Publications
external identifiers
  • pmid:35506077
  • scopus:85127303758
ISSN
2045-8932
DOI
10.1002/pul2.12041
language
English
LU publication?
yes
id
6a286722-d04d-4ae3-957c-4ba84aa595fc
date added to LUP
2022-05-16 11:30:31
date last changed
2024-04-26 13:15:48
@article{6a286722-d04d-4ae3-957c-4ba84aa595fc,
  abstract     = {{<p>Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by vasoconstriction and remodeling of the pulmonary vessels. Risk stratification in PAH could potentially be improved by including novel biomarkers related to PAH pathobiology. We aimed to investigate the relationship between extracellular matrix (ECM)-related proteins, survival, and European Society of Cardiology and European Respiratory Society (ESC/ERS) risk stratification scores in patients with PAH. Plasma samples and hemodynamics were collected from PAH patients during right heart catheterizations at diagnosis (n = 48) and early follow-up, after treatment initiation (n = 33). Plasma levels of 14 ECM-related proteins, with altered levels in PAH compared to healthy controls, were analyzed with proximity extension assays, and related to hemodynamics, transplant-free survival time, and ESC/ERS risk score. Glypican-1 levels were higher before versus after treatment initiation (p = 0.048). PAH patients with high plasma levels of matrix metalloproteinase (MMP) -2, MMP-7, MMP-9, MMP-12, perlecan, and tissue inhibitor of metalloproteinase 4 (TIMP-4) at baseline, had worse transplant-free survival (p &lt; 0.03) than patients with low levels. Hazard ratio (95% confidence interval) was for MMP-2 1.126 (1.011–1.255), perlecan 1.0099 (1.0004–1.0196), and TIMP-4 1.037 (1.003–1.071) in age and sex-adjusted Cox-regression model. MMP-2 correlated with ESC/ERS risk scores (r<sub>s</sub> = 0.34, p = 0.019), mean right atrial pressure (r<sub>s</sub> = 0.44, p = 0.002), NT-proBNP (r<sub>s</sub> = 0.49, p ≤ 0.001), and six-minute walking distance (r<sub>s</sub> = −0.34, p = 0.02). The present study indicates that high levels of MMP-2, perlecan, and TIMP-4 are associated with poor survival in PAH. High plasma MMP-2, correlated with poor prognosis in PAH. Further validation in larger studies is needed to better determine this association.</p>}},
  author       = {{Arvidsson, Mattias and Ahmed, Abdulla and Säleby, Joanna and Hesselstrand, Roger and Rådegran, Göran}},
  issn         = {{2045-8932}},
  keywords     = {{extracellular matrix; matrix metalloproteinase-2; prognosis; pulmonary arterial hypertension; risk assessment}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{SAGE Publications}},
  series       = {{Pulmonary Circulation}},
  title        = {{Plasma matrix metalloproteinase 2 is associated with severity and mortality in pulmonary arterial hypertension}},
  url          = {{http://dx.doi.org/10.1002/pul2.12041}},
  doi          = {{10.1002/pul2.12041}},
  volume       = {{12}},
  year         = {{2022}},
}