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Published on: February 16, 2016

Molecular signatures of end-stage heart failure

David Lin1, Zsuzsanna Hollander, Anna Meredith

  • 1Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Journal of Cardiac Failure
|October 4, 2011
PubMed

Insights

Blood molecular profiling reveals significant changes in chronic heart failure (CHF) patients compared to healthy controls. These findings highlight common biological themes underlying advanced heart failure, regardless of its cause.

Area of Science:

  • Cardiovascular Medicine
  • Genomics
  • Proteomics
  • Metabolomics

Background:

  • Previous chronic heart failure (CHF) studies primarily used myocardial tissue gene expression.
  • The diagnostic and prognostic utility of blood-based molecular profiling for CHF is largely unknown.
  • Proteomic and metabolomic approaches for CHF molecular characterization are underutilized.

Purpose of the Study:

  • To investigate the utility of blood-based genomic, proteomic, and metabolomic profiling in end-stage chronic heart failure (CHF).
  • To compare molecular signatures between ischemic heart disease (IHD) and nonischemic cardiomyopathy (NICM) subtypes of CHF.
  • To identify molecular differences between CHF patients and normal cardiac function (NCF) controls.

Main Methods:

  • Blood samples from 29 end-stage CHF patients (16 IHD, 13 NICM) and 20 NCF controls were analyzed.
  • Genomic (microarray), proteomic (iTRAQ), and metabolomic (NMR) platforms were employed.
  • Bioinformatic and statistical analyses identified and compared molecular signatures.

Main Results:

  • No significant gene or protein differences were found between IHD and NICM patients.
  • Significant differential expression was observed in 7,426 probe sets, 71 proteins, and 8 metabolites between CHF and NCF groups.
  • Functional enrichment analysis revealed shared biological themes and mechanisms in advanced heart failure.

Conclusions:

  • Multi-omic analyses demonstrate convergence of molecular alterations in end-stage IHD and NICM.
  • Blood-based molecular profiling can reveal significant biological changes associated with advanced CHF.
  • These findings support the potential of blood analysis for understanding CHF pathogenesis.
Abstract

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