Aerobic Exercise Training Protects Against Endothelial Dysfunction By Increasing Nitric Oxide And Hydrogen Peroxide Production In Ldl Receptor-deficient Mice

dc.creatorGuizoni
dc.creatorDaniele M.; Dorighello
dc.creatorGabriel G.; Oliveira
dc.creatorHelena C. F.; Delbin
dc.creatorMaria A.; Krieger
dc.creatorMarta H.; Davel
dc.creatorAna P.
dc.date2016
dc.datejul
dc.date2017-11-13T13:21:30Z
dc.date2017-11-13T13:21:30Z
dc.date.accessioned2018-03-29T05:54:42Z
dc.date.available2018-03-29T05:54:42Z
dc.identifierJournal Of Translational Medicine. Biomed Central Ltd, v. 14, p. , 2016.
dc.identifier1479-5876
dc.identifierWOS:000379810000001
dc.identifier10.1186/s12967-016-0972-z
dc.identifierhttps://translational-medicine.biomedcentral.com.ez88.periodicos.capes.gov.br/articles/10.1186/s12967-016-0972-z
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/327765
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1364790
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionEndothelial dysfunction associated with hypercholesterolemia is an early event in atherosclerosis characterized by redox imbalance associated with high superoxide production and reduced nitric oxide (NO) and hydrogen peroxide (H2O2) production. Aerobic exercise training (AET) has been demonstrated to ameliorate atherosclerotic lesions and oxidative stress in advanced atherosclerosis. However, whether AET protects against the early mechanisms of endothelial dysfunction in familial hypercholesterolemia remains unclear. This study investigated the effects of AET on endothelial dysfunction and vascular redox status in the aortas of LDL receptor knockout mice (LDLr-/-), a genetic model of familial hypercholesterolemia. Methods: Twelve-week-old C57BL/6J (WT) and LDLr-/- mice were divided into sedentary and exercised (AET on a treadmill 1 h/5 x per week) groups for 4 weeks. Changes in lipid profiles, endothelial function, and aortic NO, H2O2 and superoxide production were examined. Results: Total cholesterol and triglycerides were increased in sedentary and exercised LDLr-/- mice. Endothelium-dependent relaxation induced by acetylcholine was impaired in aortas of sedentary LDLr-/- mice but not in the exercised group. Inhibition of NO synthase (NOS) activity or H2O2 decomposition by catalase abolished the differences in the acetylcholine response between the animals. No changes were noted in the relaxation response induced by NO donor sodium nitroprusside or H2O2. Neuronal NOS expression and endothelial NOS phosphorylation (Ser1177), as well as NO and H2O2 production, were reduced in aortas of sedentary LDLr-/- mice and restored by AET. Incubation with apocynin increased acetylcholine-induced relaxation in sedentary, but not exercised LDLr-/- mice, suggesting a minor participation of NADPH oxidase in the endothelium-dependent relaxation after AET. Consistent with these findings, Nox2 expression and superoxide production were reduced in the aortas of exercised compared to sedentary LDLr-/- mice. Furthermore, the aortas of sedentary LDLr-/- mice showed reduced expression of superoxide dismutase (SOD) isoforms and minor participation of Cu/Zn-dependent SODs in acetylcholine-induced, endothelium-dependent relaxation, abnormalities that were partially attenuated in exercised LDLr-/- mice. Conclusion: The data gathered by this study suggest AET as a potential non-pharmacological therapy in the prevention of very early endothelial dysfunction and redox imbalance in familial hypercholesterolemia via increases in NO bioavailability and H2O2 production.
dc.description14
dc.descriptionSao Paulo Research Foundation-FAPESP [10/50323-2]
dc.descriptionUniversity of Campinas fund (FAEPX-PAPDIC Program) [25810]
dc.descriptionCoordination for the Improvement of Higher Education Personnel-CAPES
dc.descriptionBrazilian National Council for Scientific and Technological Development-CNPq
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageEnglish
dc.publisherBiomed Central Ltd
dc.publisherLondon
dc.relationJournal of Translational Medicine
dc.rightsaberto
dc.sourceWOS
dc.subjectAerobic Exercise Training
dc.subjectLdl Receptor-deficient Mice
dc.subjectFamilial Hypercholesterolemia
dc.subjectEndothelial Dysfunction
dc.subjectNitric Oxide Synthase
dc.subjectHydrogen Peroxide
dc.subjectSuperoxide Dismutase
dc.titleAerobic Exercise Training Protects Against Endothelial Dysfunction By Increasing Nitric Oxide And Hydrogen Peroxide Production In Ldl Receptor-deficient Mice
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución