Protein acetylation in the cardiorenal axis: the promise of histone deacetylase inhibitors.
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.
Bush
Erik W
EW
Gilead Colorado Inc, 3333 Walnut St, Boulder, CO 80301, USA. erik.bush@gilead.com
McKinsey
Timothy A
TA
D000107:Acetylation; D000818:Animals; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D008954:Models, Biological; D011499:Protein Processing, Post-Translational
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases