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

ESC Heart Fail. 2020 Feb;7(1):223-234. doi: 10.1002/ehf2.12560. Epub 2019 Dec 19.

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 (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.

Keywords: Biomarkers; Extracellular matrix; Haemodynamics; Heart failure; Heart transplantation; Pulmonary hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Female
  • Follow-Up Studies
  • Heart Failure / blood*
  • Heart Failure / physiopathology
  • Heart Failure / surgery
  • Heart Transplantation*
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / blood*
  • Middle Aged
  • Postoperative Period
  • Prognosis
  • Pulmonary Wedge Pressure / physiology
  • Retrospective Studies
  • Stroke Volume / physiology*
  • Ventricular Function, Left / physiology*

Substances

  • Biomarkers
  • Matrix Metalloproteinase 2