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Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload
Heart failure is associated with profound alterations of energy metabolism thought to play a major role in the progression of this syndrome. SIRT1 is a metabolic sensor of cellular energy and exerts essential functions on energy metabolism, oxidative stress response, apoptosis, or aging. Importantly...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834316/ https://www.ncbi.nlm.nih.gov/pubmed/31658614 http://dx.doi.org/10.3390/ijms20205005 |
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author | Sanz, Maria-Nieves Grimbert, Lucile Moulin, Maryline Gressette, Mélanie Rucker-Martin, Catherine Lemaire, Christophe Mericskay, Mathias Veksler, Vladimir Ventura-Clapier, Renée Garnier, Anne Piquereau, Jérôme |
author_facet | Sanz, Maria-Nieves Grimbert, Lucile Moulin, Maryline Gressette, Mélanie Rucker-Martin, Catherine Lemaire, Christophe Mericskay, Mathias Veksler, Vladimir Ventura-Clapier, Renée Garnier, Anne Piquereau, Jérôme |
author_sort | Sanz, Maria-Nieves |
collection | PubMed |
description | Heart failure is associated with profound alterations of energy metabolism thought to play a major role in the progression of this syndrome. SIRT1 is a metabolic sensor of cellular energy and exerts essential functions on energy metabolism, oxidative stress response, apoptosis, or aging. Importantly, SIRT1 deacetylates the peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), the master regulator of energy metabolism involved in mitochondrial biogenesis and fatty acid utilization. However, the exact role of SIRT1 in controlling cardiac energy metabolism is still incompletely understood and conflicting results have been obtained. We generated a cardio-specific inducible model of Sirt1 gene deletion in mice (Sirt1(ciKO)) to decipher the role of SIRT1 in control conditions and following cardiac stress induced by pressure overload. SIRT1 deficiency induced a progressive cardiac dysfunction, without overt alteration in mitochondrial content or properties. Sixteen weeks after Sirt1 deletion an increase in mitochondrial reactive oxygen species (ROS) production and a higher rate of oxidative damage were observed, suggesting disruption of the ROS production/detoxification balance. Following pressure overload, cardiac dysfunction and alteration in mitochondrial properties were exacerbated in Sirt1(ciKO) mice. Overall the results demonstrate that SIRT1 plays a cardioprotective role on cardiac energy metabolism and thereby on cardiac function. |
format | Online Article Text |
id | pubmed-6834316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68343162019-11-25 Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload Sanz, Maria-Nieves Grimbert, Lucile Moulin, Maryline Gressette, Mélanie Rucker-Martin, Catherine Lemaire, Christophe Mericskay, Mathias Veksler, Vladimir Ventura-Clapier, Renée Garnier, Anne Piquereau, Jérôme Int J Mol Sci Article Heart failure is associated with profound alterations of energy metabolism thought to play a major role in the progression of this syndrome. SIRT1 is a metabolic sensor of cellular energy and exerts essential functions on energy metabolism, oxidative stress response, apoptosis, or aging. Importantly, SIRT1 deacetylates the peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), the master regulator of energy metabolism involved in mitochondrial biogenesis and fatty acid utilization. However, the exact role of SIRT1 in controlling cardiac energy metabolism is still incompletely understood and conflicting results have been obtained. We generated a cardio-specific inducible model of Sirt1 gene deletion in mice (Sirt1(ciKO)) to decipher the role of SIRT1 in control conditions and following cardiac stress induced by pressure overload. SIRT1 deficiency induced a progressive cardiac dysfunction, without overt alteration in mitochondrial content or properties. Sixteen weeks after Sirt1 deletion an increase in mitochondrial reactive oxygen species (ROS) production and a higher rate of oxidative damage were observed, suggesting disruption of the ROS production/detoxification balance. Following pressure overload, cardiac dysfunction and alteration in mitochondrial properties were exacerbated in Sirt1(ciKO) mice. Overall the results demonstrate that SIRT1 plays a cardioprotective role on cardiac energy metabolism and thereby on cardiac function. MDPI 2019-10-10 /pmc/articles/PMC6834316/ /pubmed/31658614 http://dx.doi.org/10.3390/ijms20205005 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 Sanz, Maria-Nieves Grimbert, Lucile Moulin, Maryline Gressette, Mélanie Rucker-Martin, Catherine Lemaire, Christophe Mericskay, Mathias Veksler, Vladimir Ventura-Clapier, Renée Garnier, Anne Piquereau, Jérôme Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload |
title | Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload |
title_full | Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload |
title_fullStr | Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload |
title_full_unstemmed | Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload |
title_short | Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload |
title_sort | inducible cardiac-specific deletion of sirt1 in male mice reveals progressive cardiac dysfunction and sensitization of the heart to pressure overload |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834316/ https://www.ncbi.nlm.nih.gov/pubmed/31658614 http://dx.doi.org/10.3390/ijms20205005 |
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