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J Clin Invest. 2005 Mar;115(3):538-46.

Toward transcriptional therapies for the failing heart: chemical screens to modulate genes.

Author information

1
Myogen Inc., Westminster, Colorado 80021, USA. timothy.mckinsey@myogen.com

Abstract

In response to acute and chronic stresses, the heart frequently undergoes a remodeling process that is accompanied by myocyte hypertrophy, impaired contractility, and pump failure, often culminating in sudden death. The existence of redundant signaling pathways that trigger heart failure poses challenges for therapeutic intervention. Cardiac remodeling is associated with the activation of a pathological gene program that weakens cardiac performance. Thus, targeting the disease process at the level of gene expression represents a potentially powerful therapeutic approach. In this review, we describe strategies for normalizing gene expression in the failing heart with small molecules that control signal transduction pathways directed at transcription factors and associated chromatin-modifying enzymes.

PMID:
15765135
PMCID:
PMC1052006
DOI:
10.1172/JCI24144
[Indexed for MEDLINE]
Free PMC Article

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