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Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy

People affected by diabetes are at an increased risk of developing heart failure than their non-diabetic counterparts, attributed in part to a distinct cardiac pathology termed diabetic cardiomyopathy. Mitochondrial dysfunction and excess reactive oxygen species (ROS) have been implicated in a range...

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Autores principales: Parker, Alex M., Tate, Mitchel, Prakoso, Darnel, Deo, Minh, Willis, Andrew M., Nash, David M., Donner, Daniel G., Crawford, Simon, Kiriazis, Helen, Granata, Cesare, Coughlan, Melinda T., De Blasio, Miles J., Ritchie, Rebecca H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442993/
https://www.ncbi.nlm.nih.gov/pubmed/34539423
http://dx.doi.org/10.3389/fphys.2021.672252
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author Parker, Alex M.
Tate, Mitchel
Prakoso, Darnel
Deo, Minh
Willis, Andrew M.
Nash, David M.
Donner, Daniel G.
Crawford, Simon
Kiriazis, Helen
Granata, Cesare
Coughlan, Melinda T.
De Blasio, Miles J.
Ritchie, Rebecca H.
author_facet Parker, Alex M.
Tate, Mitchel
Prakoso, Darnel
Deo, Minh
Willis, Andrew M.
Nash, David M.
Donner, Daniel G.
Crawford, Simon
Kiriazis, Helen
Granata, Cesare
Coughlan, Melinda T.
De Blasio, Miles J.
Ritchie, Rebecca H.
author_sort Parker, Alex M.
collection PubMed
description People affected by diabetes are at an increased risk of developing heart failure than their non-diabetic counterparts, attributed in part to a distinct cardiac pathology termed diabetic cardiomyopathy. Mitochondrial dysfunction and excess reactive oxygen species (ROS) have been implicated in a range of diabetic complications and are a common feature of the diabetic heart. In this study, we sought to characterise impairments in mitochondrial structure and function in a recently described experimental mouse model of diabetic cardiomyopathy. Diabetes was induced in 6-week-old male FVB/N mice by the combination of three consecutive-daily injections of low-dose streptozotocin (STZ, each 55 mg/kg i.p.) and high-fat diet (42% fat from lipids) for 26 weeks. At study end, diabetic mice exhibited elevated blood glucose levels and impaired glucose tolerance, together with increases in both body weight gain and fat mass, replicating several aspects of human type 2 diabetes. The myocardial phenotype of diabetic mice included increased myocardial fibrosis and left ventricular (LV) diastolic dysfunction. Elevated LV superoxide levels were also evident. Diabetic mice exhibited a spectrum of LV mitochondrial changes, including decreased mitochondria area, increased levels of mitochondrial complex-III and complex-V protein abundance, and reduced complex-II oxygen consumption. In conclusion, these data suggest that the low-dose STZ-high fat experimental model replicates some of the mitochondrial changes seen in diabetes, and as such, this model may be useful to study treatments that target the mitochondria in diabetes.
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spelling pubmed-84429932021-09-16 Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy Parker, Alex M. Tate, Mitchel Prakoso, Darnel Deo, Minh Willis, Andrew M. Nash, David M. Donner, Daniel G. Crawford, Simon Kiriazis, Helen Granata, Cesare Coughlan, Melinda T. De Blasio, Miles J. Ritchie, Rebecca H. Front Physiol Physiology People affected by diabetes are at an increased risk of developing heart failure than their non-diabetic counterparts, attributed in part to a distinct cardiac pathology termed diabetic cardiomyopathy. Mitochondrial dysfunction and excess reactive oxygen species (ROS) have been implicated in a range of diabetic complications and are a common feature of the diabetic heart. In this study, we sought to characterise impairments in mitochondrial structure and function in a recently described experimental mouse model of diabetic cardiomyopathy. Diabetes was induced in 6-week-old male FVB/N mice by the combination of three consecutive-daily injections of low-dose streptozotocin (STZ, each 55 mg/kg i.p.) and high-fat diet (42% fat from lipids) for 26 weeks. At study end, diabetic mice exhibited elevated blood glucose levels and impaired glucose tolerance, together with increases in both body weight gain and fat mass, replicating several aspects of human type 2 diabetes. The myocardial phenotype of diabetic mice included increased myocardial fibrosis and left ventricular (LV) diastolic dysfunction. Elevated LV superoxide levels were also evident. Diabetic mice exhibited a spectrum of LV mitochondrial changes, including decreased mitochondria area, increased levels of mitochondrial complex-III and complex-V protein abundance, and reduced complex-II oxygen consumption. In conclusion, these data suggest that the low-dose STZ-high fat experimental model replicates some of the mitochondrial changes seen in diabetes, and as such, this model may be useful to study treatments that target the mitochondria in diabetes. Frontiers Media S.A. 2021-09-01 /pmc/articles/PMC8442993/ /pubmed/34539423 http://dx.doi.org/10.3389/fphys.2021.672252 Text en Copyright © 2021 Parker, Tate, Prakoso, Deo, Willis, Nash, Donner, Crawford, Kiriazis, Granata, Coughlan, De Blasio and Ritchie. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Parker, Alex M.
Tate, Mitchel
Prakoso, Darnel
Deo, Minh
Willis, Andrew M.
Nash, David M.
Donner, Daniel G.
Crawford, Simon
Kiriazis, Helen
Granata, Cesare
Coughlan, Melinda T.
De Blasio, Miles J.
Ritchie, Rebecca H.
Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy
title Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy
title_full Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy
title_fullStr Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy
title_full_unstemmed Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy
title_short Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy
title_sort characterisation of the myocardial mitochondria structural and functional phenotype in a murine model of diabetic cardiomyopathy
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442993/
https://www.ncbi.nlm.nih.gov/pubmed/34539423
http://dx.doi.org/10.3389/fphys.2021.672252
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