The relationship between markers of extracellular cardiac matrix turnover: infarct healing and left ventricular remodelling following primary PCI in patients with first-time STEMI

Eur Heart J. 2014 Feb;35(6):395-402. doi: 10.1093/eurheartj/eht482. Epub 2013 Nov 18.

Abstract

Aims: We investigated the temporal changes in circulating levels of markers of extracellular cardiac matrix (ECCM) turnover and their relationship with infarct size (IS), ejection fraction (EF), and left ventricular (LV) volumes, determined by serial cardiac magnetic resonance (CMR) imaging in patients with first-time ST-elevation myocardial infarction (STEMI).

Methods and results: Forty-two patients with a first-time STEMI, successfully revascularized by primary percutaneous coronary intervention (pPCI) had serum samples taken prior to pPCI, 2, 7 days, 2 months, and 1 year following STEMI for the analysis of the markers of collagen synthesis, and collagen degradation. Late enhancement and cine CMR was performed on Days 2, 7, 2 months, and 1-year post-STEMI. There was a significant increase in type I collagen degradation following STEMI that was not accompanied by an increase in collagen type I synthesis until 2 months and 1 year. In contrast to the delay in type I collagen synthesis, there was an immediate increase in type III collagen synthesis that was sustained for 1 year. N-terminal procollagen type I levels assessed prior to pPCI were predictive of adverse LV remodelling at all CMR time-points.

Conclusions: Our findings indicate a net type I collagen breakdown in the first week following STEMI compensated by an early increase in collagen type III synthesis. There is an increase in both type I and III collagen synthesis markers at 2 months and 1 year, indicating a persistent increase in collagen turnover even in these apparently successfully treated patients.

Trial registration: ClinicalTrials.gov NCT00465868.

Keywords: Collagen turnover; Extracellular cardiac matrix; Remodelling; STEMI.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Biomarkers / metabolism*
  • Collagen Type I / metabolism
  • Extracellular Matrix / metabolism*
  • Female
  • Humans
  • Magnetic Resonance Angiography
  • Male
  • Matrix Metalloproteinases / metabolism
  • Middle Aged
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Peptide Fragments / metabolism
  • Percutaneous Coronary Intervention*
  • Postoperative Care
  • Procollagen / metabolism
  • Tissue Inhibitor of Metalloproteinases / metabolism
  • Ventricular Remodeling / physiology*

Substances

  • Biomarkers
  • Collagen Type I
  • Peptide Fragments
  • Procollagen
  • Tissue Inhibitor of Metalloproteinases
  • procollagen Type I N-terminal peptide
  • Matrix Metalloproteinases

Associated data

  • ClinicalTrials.gov/NCT00465868