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Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis

Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS) generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous at...

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Autores principales: Dorighello, Gabriel G., Paim, Bruno A., Kiihl, Samara F., Ferreira, Mônica S., Catharino, Rodrigo R., Vercesi, Anibal E., Oliveira, Helena C. F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655284/
https://www.ncbi.nlm.nih.gov/pubmed/26635912
http://dx.doi.org/10.1155/2016/7843685
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author Dorighello, Gabriel G.
Paim, Bruno A.
Kiihl, Samara F.
Ferreira, Mônica S.
Catharino, Rodrigo R.
Vercesi, Anibal E.
Oliveira, Helena C. F.
author_facet Dorighello, Gabriel G.
Paim, Bruno A.
Kiihl, Samara F.
Ferreira, Mônica S.
Catharino, Rodrigo R.
Vercesi, Anibal E.
Oliveira, Helena C. F.
author_sort Dorighello, Gabriel G.
collection PubMed
description Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS) generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression) with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent.
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spelling pubmed-46552842015-12-03 Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis Dorighello, Gabriel G. Paim, Bruno A. Kiihl, Samara F. Ferreira, Mônica S. Catharino, Rodrigo R. Vercesi, Anibal E. Oliveira, Helena C. F. Oxid Med Cell Longev Research Article Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS) generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression) with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent. Hindawi Publishing Corporation 2016 2015-11-09 /pmc/articles/PMC4655284/ /pubmed/26635912 http://dx.doi.org/10.1155/2016/7843685 Text en Copyright © 2016 Gabriel G. Dorighello et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Dorighello, Gabriel G.
Paim, Bruno A.
Kiihl, Samara F.
Ferreira, Mônica S.
Catharino, Rodrigo R.
Vercesi, Anibal E.
Oliveira, Helena C. F.
Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis
title Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis
title_full Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis
title_fullStr Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis
title_full_unstemmed Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis
title_short Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis
title_sort correlation between mitochondrial reactive oxygen and severity of atherosclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655284/
https://www.ncbi.nlm.nih.gov/pubmed/26635912
http://dx.doi.org/10.1155/2016/7843685
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