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The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes

In early diabetes, hyperglycemia and the associated metabolic dysregulation promote early changes in the functional properties of cardiomyocytes, progressively leading to the appearance of the diabetic cardiomyopathy phenotype. Recently, the interplay between histone acetyltransferases (HAT) and his...

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Autores principales: Bocchi, Leonardo, Motta, Benedetta M., Savi, Monia, Vilella, Rocchina, Meraviglia, Viviana, Rizzi, Federica, Galati, Serena, Buschini, Annamaria, Lazzaretti, Mirca, Pramstaller, Peter P., Rossini, Alessandra, Stilli, Donatella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514644/
https://www.ncbi.nlm.nih.gov/pubmed/31014028
http://dx.doi.org/10.3390/ijms20081873
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author Bocchi, Leonardo
Motta, Benedetta M.
Savi, Monia
Vilella, Rocchina
Meraviglia, Viviana
Rizzi, Federica
Galati, Serena
Buschini, Annamaria
Lazzaretti, Mirca
Pramstaller, Peter P.
Rossini, Alessandra
Stilli, Donatella
author_facet Bocchi, Leonardo
Motta, Benedetta M.
Savi, Monia
Vilella, Rocchina
Meraviglia, Viviana
Rizzi, Federica
Galati, Serena
Buschini, Annamaria
Lazzaretti, Mirca
Pramstaller, Peter P.
Rossini, Alessandra
Stilli, Donatella
author_sort Bocchi, Leonardo
collection PubMed
description In early diabetes, hyperglycemia and the associated metabolic dysregulation promote early changes in the functional properties of cardiomyocytes, progressively leading to the appearance of the diabetic cardiomyopathy phenotype. Recently, the interplay between histone acetyltransferases (HAT) and histone deacetylases (HDAC) has emerged as a crucial factor in the development of cardiac disorders. The present study evaluates whether HDAC inhibition can prevent the development of cardiomyocyte contractile dysfunction induced by a short period of hyperglycemia, with focus on the potential underlying mechanisms. Cell contractility and calcium dynamics were measured in unloaded ventricular myocytes isolated from the heart of control and diabetic rats. Cardiomyocytes were either untreated or exposed to the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) for 90 min. Then, a fraction of each group of cells was used to evaluate the expression levels of proteins involved in the excitation–contraction coupling, and the cardiomyocyte metabolic activity, ATP content, and reactive oxygen species levels. SAHA treatment was able to counteract the initial functional derangement in cardiomyocytes by reducing cell oxidative damage. These findings suggest that early HDAC inhibition could be a promising adjuvant approach for preventing diabetes-induced cardiomyocyte oxidative damage, which triggers the pro-inflammatory signal cascade, mitochondrial damage, and ventricular dysfunction.
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spelling pubmed-65146442019-05-30 The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes Bocchi, Leonardo Motta, Benedetta M. Savi, Monia Vilella, Rocchina Meraviglia, Viviana Rizzi, Federica Galati, Serena Buschini, Annamaria Lazzaretti, Mirca Pramstaller, Peter P. Rossini, Alessandra Stilli, Donatella Int J Mol Sci Article In early diabetes, hyperglycemia and the associated metabolic dysregulation promote early changes in the functional properties of cardiomyocytes, progressively leading to the appearance of the diabetic cardiomyopathy phenotype. Recently, the interplay between histone acetyltransferases (HAT) and histone deacetylases (HDAC) has emerged as a crucial factor in the development of cardiac disorders. The present study evaluates whether HDAC inhibition can prevent the development of cardiomyocyte contractile dysfunction induced by a short period of hyperglycemia, with focus on the potential underlying mechanisms. Cell contractility and calcium dynamics were measured in unloaded ventricular myocytes isolated from the heart of control and diabetic rats. Cardiomyocytes were either untreated or exposed to the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) for 90 min. Then, a fraction of each group of cells was used to evaluate the expression levels of proteins involved in the excitation–contraction coupling, and the cardiomyocyte metabolic activity, ATP content, and reactive oxygen species levels. SAHA treatment was able to counteract the initial functional derangement in cardiomyocytes by reducing cell oxidative damage. These findings suggest that early HDAC inhibition could be a promising adjuvant approach for preventing diabetes-induced cardiomyocyte oxidative damage, which triggers the pro-inflammatory signal cascade, mitochondrial damage, and ventricular dysfunction. MDPI 2019-04-16 /pmc/articles/PMC6514644/ /pubmed/31014028 http://dx.doi.org/10.3390/ijms20081873 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bocchi, Leonardo
Motta, Benedetta M.
Savi, Monia
Vilella, Rocchina
Meraviglia, Viviana
Rizzi, Federica
Galati, Serena
Buschini, Annamaria
Lazzaretti, Mirca
Pramstaller, Peter P.
Rossini, Alessandra
Stilli, Donatella
The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes
title The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes
title_full The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes
title_fullStr The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes
title_full_unstemmed The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes
title_short The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes
title_sort histone deacetylase inhibitor suberoylanilide hydroxamic acid (saha) restores cardiomyocyte contractility in a rat model of early diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514644/
https://www.ncbi.nlm.nih.gov/pubmed/31014028
http://dx.doi.org/10.3390/ijms20081873
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