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Related Experiment Videos

Serial gene expression profiling in the intact human heart.

Brian D Lowes1, Ronald Zolty, Wayne A Minobe

  • 1Division of Cardiology and the Center for Computational Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Brian.Lowes@UCHSC.edu

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
|May 9, 2006
PubMed
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Serial gene expression profiling in the failing human heart is feasible. This method reveals an activated gene expression state that shifts towards improvement as heart failure phenotype improves.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genomics

Background:

  • Molecular mechanisms of contractile dysfunction and chamber remodeling in dilated cardiomyopathy remain unclear.
  • Understanding gene expression changes is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To assess the feasibility of serial global gene expression profiling in the intact human heart.
  • To correlate gene expression changes with phenotypic alterations in heart failure.

Main Methods:

  • Messenger RNA (mRNA) expression profiling using RNA from endomyocardial biopsies in 8 patients with idiopathic dilated cardiomyopathy.
  • Gene chip methodology (Affymetrix U95) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for measuring gene expression.
  • Serial measurements of gene expression and radionuclide ejection fraction over 4-12 months.

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Main Results:

  • Over 500 genes showed altered mRNA abundance (241 increased, 331 decreased).
  • High agreement was observed between gene chip and RT-PCR measurements.
  • Serial sampling showed less variance than cross-sectional sampling, highlighting dynamic changes.

Conclusions:

  • Serial gene expression profiling is feasible in the human heart and offers advantages over cross-sectional studies.
  • The failing heart exhibits an activated gene expression state.
  • Phenotypic improvement in heart failure is associated with a net reduction in gene expression.