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.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
dc.subjectAortic valvefr
dc.subjectLeft ventriclefr
dc.subjectAortic regurgitationfr
dc.subjectVolume overloadfr
dc.titleBlockade of the acute activation of mTOR complex 1 decreases hypertrophy development in rats with severe aortic valve
dc.typeCOAR1_1::Texte::Périodique::Revue::Contribution à un journal::Article::Article de recherchefr
dcterms.bibliographicCitationSpringerPlus, Vol. 4 (1), 1–13 (2015)fr
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.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
bul.rights.periodeEmbargo0 moisfr
Collection:Articles publiés dans des revues avec comité de lecture

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