Research ArticleHeart Failure

Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism

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Science Translational Medicine  07 Feb 2018:
Vol. 10, Issue 427, eaao0144
DOI: 10.1126/scitranslmed.aao0144

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Deacetylation and diastolic dysfunction

Systolic heart failure (heart failure with reduced ejection fraction) manifests as insufficient blood pumping due to contractile dysfunction. Impaired cardiac relaxation also contributes to a form of heart failure termed heart failure with preserved ejection fraction. Jeong et al. tested whether histone deacetylase inhibition, which has shown efficacy in some models of systolic heart failure, could prevent diastolic dysfunction. Inhibitor treatment improved cardiac relaxation without altering blood pressure or fibrosis in rodent models of hypertension- and aging-induced diastolic dysfunction with preserved ejection fraction. The authors determined that acetylation/deacetylation of myofibrils directly altered relaxation but not contraction, suggesting a mechanism for the development of diastolic dysfunction and a potential therapeutic target.