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Prolargin and matrix metalloproteinase-2 in heart failure after heart transplantation and their association with haemodynamics

Ahmed, Abdulla LU ; Ahmed, Salaheldin LU ; Arvidsson, Mattias LU ; Bouzina, Habib LU ; Lundgren, Jakob LU and Rådegran, Göran LU (2019) In ESC Heart Failure
Abstract

AIMS: Remodelling of the extracellular matrix (ECM) is a key mechanism involved in the development and progression of heart failure (HF) but also functional in associated pulmonary hypertension (PH). Our aim was to identify plasma ECM proteins associated to end-stage HF and secondary PH in relation to haemodynamics, before and after heart transplantation (HT).

METHODS AND RESULTS: Twenty ECM plasma proteins were analysed with proximity extension assay in 20 controls and 26 HF patients pre-HT and 1 year post-HT. Right heart catherization haemodynamics were assessed in the patients during the preoperative evaluation and at the 1 year follow-up post-HT. Plasma levels of prolargin and matrix metalloproteinase-2 (MMP-2) were elevated... (More)

AIMS: Remodelling of the extracellular matrix (ECM) is a key mechanism involved in the development and progression of heart failure (HF) but also functional in associated pulmonary hypertension (PH). Our aim was to identify plasma ECM proteins associated to end-stage HF and secondary PH in relation to haemodynamics, before and after heart transplantation (HT).

METHODS AND RESULTS: Twenty ECM plasma proteins were analysed with proximity extension assay in 20 controls and 26 HF patients pre-HT and 1 year post-HT. Right heart catherization haemodynamics were assessed in the patients during the preoperative evaluation and at the 1 year follow-up post-HT. Plasma levels of prolargin and matrix metalloproteinase-2 (MMP-2) were elevated (P < 0.0001) in HF patients compared with controls and decreased (P < 0.0001) post-HT towards controls' levels. The decrease in prolargin post-HT correlated with improved mean right atrial pressure (rs = 0.63; P = 0.00091), stroke volume index (rs = -0.73; P < 0.0001), cardiac index (rs = -0.64; P = 0.00057), left ventricular stroke work index (rs = -0.49; P = 0.015), and N-terminal pro brain natriuretic peptide (rs = 0.7; P < 0.0001). The decrease in MMP-2 post-HT correlated with improved mean pulmonary artery pressure (rs = 0.58; P = 0.0025), mean right atrial pressure (rs = 0.56; P = 0.0046), pulmonary artery wedge pressure (rs = 0.48; P = 0.016), and N-terminal pro brain natriuretic peptide (rs = 0.56; P = 0.0029).

CONCLUSIONS: The normalization pattern in HF patients of plasma prolargin and MMP-2 post-HT towards controls' levels and their associations with improved haemodynamics indicate that prolargin and MMP-2 may reflect, in part, the aberrant ECM remodelling involved in the pathophysiology of HF and associated PH. Their potential clinical use as biomarkers or targets for future therapy in HF and related PH remains to be investigated.

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author
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publication status
epub
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in
ESC Heart Failure
publisher
John Wiley and Sons Ltd
external identifiers
  • scopus:85076719061
  • pmid:31858729
ISSN
2055-5822
DOI
10.1002/ehf2.12560
language
English
LU publication?
yes
additional info
© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
id
5730caf9-7d38-4e7f-975c-4aecc6c54871
date added to LUP
2020-01-09 23:58:10
date last changed
2020-07-08 05:10:30
@article{5730caf9-7d38-4e7f-975c-4aecc6c54871,
  abstract     = {<p>AIMS: Remodelling of the extracellular matrix (ECM) is a key mechanism involved in the development and progression of heart failure (HF) but also functional in associated pulmonary hypertension (PH). Our aim was to identify plasma ECM proteins associated to end-stage HF and secondary PH in relation to haemodynamics, before and after heart transplantation (HT).</p><p>METHODS AND RESULTS: Twenty ECM plasma proteins were analysed with proximity extension assay in 20 controls and 26 HF patients pre-HT and 1 year post-HT. Right heart catherization haemodynamics were assessed in the patients during the preoperative evaluation and at the 1 year follow-up post-HT. Plasma levels of prolargin and matrix metalloproteinase-2 (MMP-2) were elevated (P &lt; 0.0001) in HF patients compared with controls and decreased (P &lt; 0.0001) post-HT towards controls' levels. The decrease in prolargin post-HT correlated with improved mean right atrial pressure (rs = 0.63; P = 0.00091), stroke volume index (rs = -0.73; P &lt; 0.0001), cardiac index (rs = -0.64; P = 0.00057), left ventricular stroke work index (rs = -0.49; P = 0.015), and N-terminal pro brain natriuretic peptide (rs = 0.7; P &lt; 0.0001). The decrease in MMP-2 post-HT correlated with improved mean pulmonary artery pressure (rs = 0.58; P = 0.0025), mean right atrial pressure (rs = 0.56; P = 0.0046), pulmonary artery wedge pressure (rs = 0.48; P = 0.016), and N-terminal pro brain natriuretic peptide (rs = 0.56; P = 0.0029).</p><p>CONCLUSIONS: The normalization pattern in HF patients of plasma prolargin and MMP-2 post-HT towards controls' levels and their associations with improved haemodynamics indicate that prolargin and MMP-2 may reflect, in part, the aberrant ECM remodelling involved in the pathophysiology of HF and associated PH. Their potential clinical use as biomarkers or targets for future therapy in HF and related PH remains to be investigated.</p>},
  author       = {Ahmed, Abdulla and Ahmed, Salaheldin and Arvidsson, Mattias and Bouzina, Habib and Lundgren, Jakob and Rådegran, Göran},
  issn         = {2055-5822},
  language     = {eng},
  month        = {12},
  publisher    = {John Wiley and Sons Ltd},
  series       = {ESC Heart Failure},
  title        = {Prolargin and matrix metalloproteinase-2 in heart failure after heart transplantation and their association with haemodynamics},
  url          = {http://dx.doi.org/10.1002/ehf2.12560},
  doi          = {10.1002/ehf2.12560},
  year         = {2019},
}