title: Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis.
abstract: 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.
authors.affiliation: Department of Structural and Functional Biology, Biology Institute, State University of Campinas, 13083-862 Campinas, SP, Brazil.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Dorighello
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, 13083-887 Campinas, SP, Brazil.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Paim
authors.affiliation: Department of Statistics, Institute of Mathematics, Statistic and Scientific Computation, State University of Campinas, 13083-859 Campinas, SP, Brazil.
authors.forename: Samara F
authors.initials: SF
authors.lastname: Kiihl
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, 13083-887 Campinas, SP, Brazil.
authors.forename: Mônica S
authors.initials: MS
authors.lastname: Ferreira
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, 13083-887 Campinas, SP, Brazil.
authors.forename: Rodrigo R
authors.initials: RR
authors.lastname: Catharino
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, 13083-887 Campinas, SP, Brazil.
authors.forename: Anibal E
authors.initials: AE
authors.lastname: Vercesi
authors.affiliation: Department of Structural and Functional Biology, Biology Institute, State University of Campinas, 13083-862 Campinas, SP, Brazil.
authors.forename: Helena C F
authors.initials: HC
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009249:NADP / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D009249:NADP; D002784:Cholesterol