Targeting histone deacetylases for heart failure.
BACKGROUND
Stresses such as chronic hypertension and myocardial infarction can trigger the heart to undergo a remodeling process characterized by myocyte hypertrophy, myocyte death and fibrosis, often resulting in impaired cardiac function and heart failure. Recent studies suggest key roles for histone deacetylases (HDACs) in the control of pathological cardiac remodeling.


OBJECTIVE
Here, we review these target validation experiments and highlight non-cardiac functions of HDACs that will need to be addressed during development of HDAC-directed therapies for heart failure.


CONCLUSIONS
HDACs are unique and attractive therapeutic targets for heart failure because of their positions far downstream in pathological signaling cascades. Confirmation of the validity and viability of approaches aimed at HDACs awaits in vivo proof-of-concept testing with novel small molecule regulators of these enzymes.
Bush
Erik W
EW
Gilead Colorado, Inc., 3333 Walnut Street, Boulder, Colorado 80301, USA. erik.bush@gilead.com
McKinsey
Timothy A
TA
D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000503:physiopathology; D016503:Drug Delivery Systems; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020257:Ventricular Remodeling / Q000187:drug effects
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases