Circulating multimarker profile of patients with symptomatic heart failure supports enhanced fibrotic degradation and decreased angiogenesis

Biomarkers. 2016;21(1):91-7. doi: 10.3109/1354750X.2015.1118539. Epub 2015 Dec 15.

Abstract

Background: Heart failure (HF) involves myocardial fibrosis and dysregulated angiogenesis.

Objective: We explored whether biomarkers of fibrosis and angiogenesis correlate with HF severity.

Methods: Biomarkers of fibrosis [procollagen types I and III (PIP and P3NP), carboxyterminal-telopeptide of type I collagen (ICTP), matrix metalloproteases (MMP2 and MMP9), tissue inhibitor of MMP1 (TIMP1)]; and angiogenesis [placental growth factor (PGF), vascular endothelial growth factor (VEGF), soluble Fms-like tyrosine kinase-1 (sFlt1)] were measured in 52 HF patients and 19 controls.

Results: P3NP, ICTP, MMP2, TIMP1, PGF, and sFlt1 levels were elevated in HF, while PIP/ICTP, PGF/sFlt1, and VEGF/sFlt1 ratios were reduced. PIP/ICTP, MMP-9/TIMP1, and VEGF/sFlt1 ratios were lowest among patients with severe HF.

Conclusions: Severe HF is associated with collagen breakdown and reduced angiogenesis. A multimarker approach may guide therapeutic targeting of fibrosis and angiogenesis in HF.

Keywords: Cardiovascular disease; growth factors/cytokines/inflammatory mediators; hematology.

MeSH terms

  • Aged
  • Angiogenic Proteins / blood
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Fibrosis
  • Heart Failure / blood*
  • Humans
  • Male
  • Middle Aged
  • Myocardium / pathology*
  • Neovascularization, Physiologic
  • Prospective Studies

Substances

  • Angiogenic Proteins
  • Biomarkers