Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

Joao Pedro Ferreira, Jean-Loup Machu, Nicolas Girerd, Frederic Jaisser, Thomas Thum, Javed Butler, Arantxa Gonzalez, Javier Diez, Stephane Heymans, Kenneth McDonald, Mariann Gyongyosi, Hueseyin Firat, Patrick Rossignol, Anne Pizard, Faiez Zannad*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Aims Myocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European-Commission-funded 'FIBROTARGETS' is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti-fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure. Methods and results The FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community-based population cohorts, cardiovascular risk cohorts, and heart failure cohorts. Conclusions The FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific 'fibrotic' phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti-fibrotic therapies for heart failure.
Original languageEnglish
Pages (from-to)139-148
Number of pages10
JournalEsc heart failure
Volume5
Issue number1
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • Myocardial fibrosis
  • Fibrotic bioprofiles
  • Heart failure
  • GELATINASE-ASSOCIATED LIPOCALIN
  • COLLAGEN CROSS-LINKING
  • MICRORNA SIGNATURES DIFFERENTIATE
  • EXTRACELLULAR-MATRIX TURNOVER
  • CONGESTIVE-HEART-FAILURE
  • CARDIOVASCULAR-DISEASE
  • HYPERTENSIVE PATIENTS
  • CARDIAC-FUNCTION
  • CIRCULATING BIOMARKERS
  • DIASTOLIC DYSFUNCTION
  • Cardiomyopathies/metabolism
  • Biomarkers/analysis
  • Humans
  • Animals
  • Myocardium/metabolism
  • Research Design
  • Fibrosis/metabolism

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