Transcriptomic profiling of the canine tachycardia-induced heart failure model: Global comparison to human and murine heart failure

Zhong Gao, Hai Xu, Deborah DiSilvestre, Victoria L. Halperin, Richard Tunin, Yanli Tian, Wayne Yu, Raimond L. Winslow, Gordon F. Tomaselli

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Alterations of cardiac gene expression are central to ventricular dysfunction in human heart failure (HF). The canine tachycardia pacing-induced HF model is known to reproduce the main hemodynamic, echocardiographic and electrophysiological changes observed in human HF. In this study, we use this HF model to compare gene expression profiles in the left and right ventricles (LV, RV) of normal and end-stage failing canine hearts and compare the transcription profiles to those in human and murine models of HF. In end-stage HF, the LV exhibits down regulation of genes involved in energy production, cardiac contraction, and modulation of excitation-contraction coupling as compared with normal LV. The majority of transcriptomic changes between normal and end-stage canine HF were shared by the RV and LV. Genes down regulated only in the LV included those involved in aerobic energy production pathways, regulation of actin filament length, and enzyme-linked receptor protein signaling pathways. In normal canine hearts, genes encoding specific components of the contractile apparatus exhibit LV-RV asymmetric expression patterns; in failing hearts, cardiac fetal transcription factors MEF2 and MITF and the stress-responsive transcription factor ATF4 showed interventricular differences in expression. The comparison among the canine tachypacing, mouse transgenic, and human HF reveals that human disease involves down regulation of genes in a broad range of biological processes while experimentally induced HF is associated with down regulation of energy pathways, and that human ischemic HF and canine HF share a similar over representation of transcriptional pathways in the up regulated genes. This study provides insights into the molecular pathways leading to end-stage tachycardia-induced HF, and into global transcriptomic differences between the animal HF models and human HF.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume40
Issue number1
DOIs
Publication statusPublished - Jan 1 2006
Externally publishedYes

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Keywords

  • Cardiomyopathy
  • Gene expression
  • Gene ontology
  • Microarray
  • Pacing
  • RT-PCR
  • Remodeling
  • Tachycardia-induced heart failure
  • Transcriptome

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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