Transcriptome, proteome, and metabolome in dyssynchronous heart failure and CRT

Andreas S. Barth, Khalid Chakir, David A. Kass, Gordon F. Tomaselli

Research output: Contribution to journalReview article

13 Scopus citations

Abstract

Cardiac resynchronization therapy reduces morbidity and mortality in patients with symptomatic systolic heart failure (New York Heart Association class III or IV) and ventricular conduction delay. The current review focuses on how high-throughput technologies including gene expression profiling and proteomics have helped in our understanding of the pathophysiology of electromechanical dyssynchrony and the molecular mechanisms by which cardiac resynchronization therapy (CRT) exerts its beneficial effects. Comparing gene expression changes in earlyactivated anterior vs. late-activated lateral left ventricular myocardium in a large animal model of dyssynchronous heart failure, we demonstrated a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, as changes in gene expression were primarily observed in the early-activated anterior left ventricular myocardium. This increase in regional heterogeneity of gene expression within the left ventricle was reversed by CRT. Specifically, CRT remodeled transcripts with metabolic and cell signaling function, which was corroborated by protein data. In addition, high-throughput or "omic" techniques also hold great promise to identify key pathways and biomarkers that are regulated differentially in CRT responders vs. nonresponders.

Original languageEnglish (US)
Pages (from-to)180-187
Number of pages8
JournalJournal of Cardiovascular Translational Research
Volume5
Issue number2
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

Keywords

  • Cardiac resynchronization therapy
  • Functional genomics
  • Gene expression
  • Heart failure
  • Proteomics

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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