Blockade of the acute activation of mTOR complex 1 decreases hypertrophy development in rats with severe aortic valve regurgitation.

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dc.contributor.authorDrolet, Marie-Claude-
dc.contributor.authorDesbiens-Brassard, Vincent-
dc.contributor.authorRoussel, Élise-
dc.contributor.authorTu, Véronique-
dc.contributor.authorCouët, Jacques-
dc.contributor.authorArsenault, Marie-
dc.date.accessioned2017-11-16T21:11:50Z-
dc.date.available2017-11-16T21:11:50Z-
dc.date.issued2015-08-20-
dc.identifier.issn2193-1801fr
dc.identifier.urihttp://hdl.handle.net/20.500.11794/15871-
dc.description.abstractBackground : Hypertrophy (H) is an adaptive response of the heart to a hemodynamic overload. Severe left ventricular (LV) volume overload (VO) from valve regurgitations (aortic (AR) or mitral regurgitation) leads to eccentric LVH. Increased protein turnover is a major event during development of LVH and the mechanistic target of rapamycin (mTOR) is a key molecule for its control. The role of mTOR inhibition in the development of LVH using rapamycin for relatively short periods of time (days to a few weeks) has been studied in the past in pressure overload models but not in VO models. We investigated if mTOR pathway was activated during LVH development in a model of severe VO (AR) in rats and if a rapamycin treatment can slow heart remodeling in this situation. Methods and Results : Male rats with severe AR were studied acutely at 2 days, at 8 weeks (compensated phase) and 6 months (late phase) after VO induction. mTOR complex (mTORC) 1 (ribosomal S6 protein phosphorylation) was activated early after AR induction but not later in the disease whereas mTORC2 activity levels (Akt phosphorylation at Ser473) remained stable. We observed that a moderate dose of rapamycin (2 mg/kg/day; orally) for 8 weeks prevented severe LVH caused by AR (−46 %: p < 0.001). Rapamycin treatment specifically inhibited LV mTORC1 without altering mTORC2 activity at 8 weeks. Rapamycin also prevented cardiac myocyte hypertrophy caused by AR. Conclusion : Rapamycin slows hypertrophy in LV VO by inhibiting early activation of mTORC1 without modulating mTORC2.fr
dc.languageengfr
dc.publisherSpringerfr
dc.subjectHeartfr
dc.subjectAortic valvefr
dc.subjectHypertrophyfr
dc.subjectLeft ventriclefr
dc.subjectAortic regurgitationfr
dc.subjectVolume overloadfr
dc.subjectRapamycinfr
dc.subjectmTORfr
dc.titleBlockade of the acute activation of mTOR complex 1 decreases hypertrophy development in rats with severe aortic valve regurgitation.fr
dc.typeCOAR1_1::Texte::Périodique::Revue::Contribution à un journal::Article::Article de recherchefr
dcterms.bibliographicCitationSpringerPlus, Vol. 4 (1), 1–13 (2015)fr
dc.identifier.doi10.1186/s40064-015-1230-1fr
dc.identifier.pubmed4542859fr
dc.subject.rvmSirolimusfr
dc.subject.rvmCœur -- Ventricule gauche -- Hypertrophiefr
dc.subject.rvmCœur -- Valvules -- Maladiesfr
dc.subject.rvmRats (Animaux de laboratoire)fr
dc.subject.rvmSérine/thréonine kinases TORfr
rioxxterms.versionVersion of Recordfr
rioxxterms.version_of_recordhttps://doi.org/10.1186/s40064-015-1230-1fr
rioxxterms.project.funder_nameCanadian Institutes of Health Researchfr
rioxxterms.project.funder_nameHeart and Stroke Foundation of Canadafr
rioxxterms.project.funder_nameInstitut universitaire de cardiologie et de pneumologie de Québec Foundationfr
ali.license_refAttribution CC BYfr
ali.license_ref.start_date2017-11-14fr
bul.rights.periodeEmbargo0 moisfr
Collection:Articles publiés dans des revues avec comité de lecture

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