TY - JOUR
T1 - Toward transcriptional therapies for the failing heart
T2 - Chemical screens to modulate genes
AU - McKinsey, Timothy A.
AU - Olson, Eric N.
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI24144
DO - 10.1172/JCI24144
M3 - Review article
C2 - 15765135
AN - SCOPUS:14644431730
SN - 0021-9738
VL - 115
SP - 538
EP - 546
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -