Alterations in apoptotic signaling in human idiopathic cardiomyopathic hearts in failure

Charles Steenbergen, Cynthia A. Afshari, John G. Petranka, Jennifer Collins, Karla Martin, Lee Bennett, Astrid Haugen, Pierre Bushel, Elizabeth Murphy

Research output: Contribution to journalArticlepeer-review

Abstract

Dilated cardiomyopathy, a disease of unknown etiology and pathogenesis, is associated with heart failure and compensatory hypertrophy. Although cell and animal models suggest a role for altered gene expression in the transition to heart failure, there is a paucity of data derived from the study of human heart tissue. In this study, we used DNA microarray profiling to investigate changes in the expression of genes involved in apoptosis that occur in human idiopathic dilated cardiomyopathic hearts that had progressed to heart failure. We observed altered gene expression consistent with a proapoptotic shift in the TNF-α signaling pathway. Specifically, we found decreased expression of TNF-α- and NF-κB-induced antiapoptotic genes such as growth arrest and DNA damage-inducible (GADD)45β, Flice inhibitory protein (FLIP), and TNF-induced protein 3 (A20). Consistent with a role for apoptosis in heart failure, we also observed a significant decrease in phosphorylation of BAD at Ser-112. This study identifies several pathways that are altered in human heart failure and provides new targets for therapy.

Original languageEnglish (US)
Pages (from-to)H268-H276
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number1 53-1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • BAD
  • GADD45β
  • Gene profiling
  • TNF-α

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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