Integrative Effect of Carvedilol and Aerobic Exercise Training Therapies on Improving Cardiac Contractility and Remodeling in Heart Failure Mice

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dc.contributor.author Vanzelli, Andrea S.
dc.contributor.author Medeiros, Alessandra [UNIFESP]
dc.contributor.author Rolim, Natale
dc.contributor.author Bartholomeu, Jan B.
dc.contributor.author Cunha, Telma F.
dc.contributor.author Bechara, Luiz G.
dc.contributor.author Gomes, Eneas R. M.
dc.contributor.author Mattos, Katt C.
dc.contributor.author Sirvente, Raquel
dc.contributor.author Salemi, Vera
dc.contributor.author Mady, Charles
dc.contributor.author Negrao, Carlos E.
dc.contributor.author Guatimosim, Silvia
dc.contributor.author Brum, Patricia C.
dc.date.accessioned 2016-01-24T14:31:38Z
dc.date.available 2016-01-24T14:31:38Z
dc.date.issued 2013-05-01
dc.identifier http://dx.doi.org/10.1371/journal.pone.0062452
dc.identifier.citation Plos One. San Francisco: Public Library Science, v. 8, n. 5, 8 p., 2013.
dc.identifier.issn 1932-6203
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/36250
dc.description.abstract The use of b-blockers is mandatory for counteracting heart failure (HF)-induced chronic sympathetic hyperactivity, cardiac dysfunction and remodeling. Importantly, aerobic exercise training, an efficient nonpharmacological therapy to HF, also counteracts sympathetic hyperactivity in HF and improves exercise tolerance and cardiac contractility; the latter associated with changes in cardiac Ca2+ handling. This study was undertaken to test whether combined b-blocker and aerobic exercise training would integrate the beneficial effects of isolated therapies on cardiac structure, contractility and cardiomyocyte Ca2+ handling in a genetic model of sympathetic hyperactivity-induced HF (alpha(2A)/alpha 2C(-)adrenergic receptor knockout mice, KO). We used a cohort of 5-7 mo male wild-type (WT) and congenic mice (KO) with C57Bl6/J genetic background randomly assigned into 5 groups: control (WT), saline-treated KO (KOS), exercise trained KO (KOT), carvedilol-treated KO (KOC) and, combined carvedilol-treated and exercise-trained KO (KOCT). Isolated and combined therapies reduced mortality compared with KOS mice. Both KOT and KOCT groups had increased exercise tolerance, while groups receiving carvedilol had increased left ventricular fractional shortening and reduced cardiac collagen volume fraction compared with KOS group. Cellular data confirmed that cardiomyocytes from KOS mice displayed abnormal Ca2+ handling. KOT group had increased intracellular peak of Ca2+ transient and reduced diastolic Ca2+ decay compared with KOS group, while KOC had increased Ca2+ decay compared with KOS group. Notably, combined therapies re-established cardiomyocyte Ca2+ transient paralleled by increased SERCA2 expression and SERCA2: PLN ratio toward WT levels. Aerobic exercise trained increased the phosphorylation of PLN at Ser16 and Thr17 residues in both KOT and KOCT groups, but carvedilol treatment reduced lipid peroxidation in KOC and KOCT groups compared with KOS group. the present findings provide evidence that the combination of carvedilol and aerobic exercise training therapies lead to a better integrative outcome than carvedilol or exercise training used in isolation. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorship Conselho Nacional de Pesquisa e Desenvolvimento
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 8
dc.language.iso eng
dc.publisher Public Library Science
dc.relation.ispartof Plos One
dc.rights Acesso aberto
dc.title Integrative Effect of Carvedilol and Aerobic Exercise Training Therapies on Improving Cardiac Contractility and Remodeling in Heart Failure Mice en
dc.type Artigo
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Dept Circulat & Med Imaging
dc.contributor.institution KG Jebsen Ctr Exercise Med
dc.contributor.institution Universidade Federal de Minas Gerais (UFMG)
dc.description.affiliation Univ São Paulo, Sch Phys Educ & Sport, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Biosci, Santos, Brazil
dc.description.affiliation Dept Circulat & Med Imaging, Trondheim, Norway
dc.description.affiliation KG Jebsen Ctr Exercise Med, Trondheim, Norway
dc.description.affiliation Univ Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil
dc.description.affiliation Univ São Paulo, Heart Inst InCor, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biosci, Santos, Brazil
dc.description.sponsorshipID FAPESP: FAPESP:2010/50048-1
dc.description.sponsorshipID FAPESP: 06/56123-0
dc.description.sponsorshipID CNPq: 302201/2011-4
dc.identifier.file WOS000319167000045.pdf
dc.identifier.doi 10.1371/journal.pone.0062452
dc.description.source Web of Science
dc.identifier.wos WOS:000319167000045



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