Heart failure with preserved ejection fraction induces molecular, mitochondrial, histological, and functional alterations in rat respiratory and limb skeletal muscle

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dc.contributor.authorBowen, T. Scott
dc.contributor.authorRolim, Natale P. L.
dc.contributor.authorFischer, Tina
dc.contributor.authorBaekkerud, Fredrik H.
dc.contributor.authorMedeiros, Alessandra [UNIFESP]
dc.contributor.authorWerner, Sarah
dc.contributor.authorBronstad, Eivind
dc.contributor.authorRognmo, Oivind
dc.contributor.authorMangner, Norman
dc.contributor.authorLinke, Axel
dc.contributor.authorSchuler, Gerhard
dc.contributor.authorSilva, Gustavo J. J.
dc.contributor.authorWisloff, Ulrik
dc.contributor.authorAdams, Volker
dc.contributor.authorOptimex Study Grp
dc.contributor.institutionUniv Leipzig
dc.contributor.institutionNorwegian Univ Sci & Technol
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:40:05Z
dc.date.available2016-01-24T14:40:05Z
dc.date.issued2015-03-01
dc.description.abstractAimsPeripheral muscle dysfunction is a key mechanism contributing to exercise intolerance (i.e. breathlessness and fatigue) in heart failure patients with preserved ejection fraction (HFpEF); however, the underlying molecular and cellular mechanisms remain unknown. We therefore used an animal model to elucidate potential molecular, mitochondrial, histological, and functional alterations induced by HFpEF in the diaphragm and soleus, while also determining the possible benefits associated with exercise training.Methods and resultsFemale Dahl salt-sensitive rats were fed a low (CON; n = 10) or high salt (HFpEF; n = 11) diet of 0.3% or 8% NaCl, respectively, or a high salt diet in combination with treadmill exercise training (n = 11). Compared with low-salt rats, high-salt rats developed (P < 0.05) HFpEF. Compared with CON, the diaphragm of HFpEF rats demonstrated (P < 0.05): a fibre type shift from fast-to-slow twitch; fibre atrophy; a decreased pro-oxidative but increased anti-oxidant capacity; reduced proteasome activation; impaired in situ mitochondrial respiration; and in vitro muscle weakness and increased fatigability. the soleus also demonstrated numerous alterations (P < 0.05), including fibre atrophy, decreased anti-oxidant capacity, reduced mitochondrial density, and increased fatigability. Exercise training, however, prevented mitochondrial and functional impairments in both the diaphragm and soleus (P < 0.05).ConclusionOur findings are the first to demonstrate that HFpEF induces significant molecular, mitochondrial, histological, and functional alterations in the diaphragm and soleus, which were attenuated by exercise training. These data therefore reveal novel mechanisms and potential therapeutic treatments of exercise intolerance in HFpEF.en
dc.description.affiliationUniv Leipzig, Ctr Heart, Dept Internal Med & Cardiol, D-04289 Leipzig, Germany
dc.description.affiliationNorwegian Univ Sci & Technol, Fac Med, Dept Circulat & Med Imaging, KG Jebsen Ctr Exercise Med, N-7034 Trondheim, Norway
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biosci, Santos, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biosci, Santos, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipEuropean Commission
dc.description.sponsorshipAlexander von Humboldt Foundation
dc.description.sponsorshipIDEuropean Commission: EU 602405-2
dc.format.extent263-272
dc.identifierhttp://dx.doi.org/10.1002/ejhf.239
dc.identifier.citationEuropean Journal of Heart Failure. Hoboken: Wiley-Blackwell, v. 17, n. 3, p. 263-272, 2015.
dc.identifier.doi10.1002/ejhf.239
dc.identifier.issn1388-9842
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38777
dc.identifier.wosWOS:000351079800006
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofEuropean Journal of Heart Failure
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectDiastolic dysfunctionen
dc.subjectDiaphragmen
dc.subjectExercise trainingen
dc.subjectMitochondrial respirationen
dc.subjectSoleusen
dc.titleHeart failure with preserved ejection fraction induces molecular, mitochondrial, histological, and functional alterations in rat respiratory and limb skeletal muscleen
dc.typeinfo:eu-repo/semantics/article
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