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(Circulation Research. 2010;106:272.)
© 2010 American Heart Association, Inc.

Reviews

Protein Acetylation in the Cardiorenal Axis

The Promise of Histone Deacetylase Inhibitors

Erik W. Bush, Timothy A. McKinsey

From Gilead Colorado Inc, Boulder, Colo.

Correspondence to Erik W. Bush or Timothy A. McKinsey, Gilead Colorado Inc, 3333 Walnut St, Boulder, CO 80301. E-mail erik.bush{at}gilead.com or timothy.mckinsey@gilead.com

This Review is part of a thematic series on Novel Posttranslational Modifications of Proteins and Their Cardiovascular Significance, which includes the following articles:

The Emerging Characterization of Lysine Residue Deacetylation on The Modulation of Mitochondrial Function and Cardiovascular Biology [2009;105:830–841]

Protein Acetylation in the Cardiorenal Axis: The Promise of Histone Deacetylase Inhibitors

Protein S-Nitrosylation and Cardioprotection [2010;106:285–296]

S-Nitrosylation and Cardiovascular Signaling

S-Nitrosylation and Cardiac Ischemia

Glycosylation and Cardiovascular Signaling

Ubiquitination and Cardiovascular Signaling
Elizabeth Murphy Guest Editor

Abstract: Acetylation of histone and nonhistone proteins provides a key mechanism for controlling signaling and gene expression in heart and kidney. Pharmacological inhibition of protein deacetylation with histone deacetylase (HDAC) inhibitors has shown promise in preclinical models of cardiovascular and renal disease. Efficacy of HDAC inhibitors appears to be governed by pleiotropic salutary actions on a variety of cell types and pathophysiological processes, including myocyte hypertrophy, fibrosis, inflammation and epithelial-to-mesenchymal transition, and occurs at compound concentrations below the threshold required to elicit toxic side effects. We review the roles of acetylation/deacetylation in the heart and kidney and provide rationale for extending HDAC inhibitors into clinical testing for indications involving these organs.

Key Words: acetylation • histone deacetylase • heart failure • kidney failure • fibrosis