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

Timothy A. McKinsey, Eric N. Olson

Research output: Contribution to journalReview article

216 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)538-546
Number of pages9
JournalJournal of Clinical Investigation
Volume115
Issue number3
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Medicine(all)

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