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Crest maturation at the cardiomyocyte surface contributes to a new late postnatal development stage that controls the diastolic function of the adult heart

dc.rights.licenseopenen_US
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
hal.structure.identifierCentre Hospitalier Universitaire de Toulouse [CHU Toulouse]
dc.contributor.authorKARSENTY, Clément
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
hal.structure.identifierCentre Hospitalier Universitaire de Toulouse [CHU Toulouse]
dc.contributor.authorGUILBEAU-FRUGIER, Céline
hal.structure.identifierUniversity of Virginia School of Medicine [US]
dc.contributor.authorGENET, Gaël
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorSEGUELAS, Marie-Hélène
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorALZIEU, Philippe
hal.structure.identifierPhysiologie & médecine expérimentale du Cœur et des Muscles [U 1046] [PhyMedExp]
dc.contributor.authorCAZORLA, Olivier
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorMONTAGNER, Alexandra
hal.structure.identifierInstitut de Génétique et Développement de Rennes [IGDR]
dc.contributor.authorBLUM, Yuna
dc.contributor.authorDUBROCA, Caroline
dc.contributor.authorMAUPOINT, Julie
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
hal.structure.identifierCentre Hospitalier Universitaire de Toulouse [CHU Toulouse]
dc.contributor.authorTRAMUNT, Blandine
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorCAUQUIL, Marie
dc.contributor.authorSULPICE, Thierry
hal.structure.identifierPhysiologie & médecine expérimentale du Cœur et des Muscles [U 1046] [PhyMedExp]
dc.contributor.authorRICHARD, Sylvain
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorARCUCCI, Silvia
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorFLORES-FLORES, Remy
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorPATALUCH, Nicolas
hal.structure.identifierCentre Hospitalier Universitaire de Toulouse [CHU Toulouse]
hal.structure.identifierUniversité Toulouse III - Paul Sabatier [UT3]
dc.contributor.authorMONTORIOL, Romain
hal.structure.identifierPhysiologie & médecine expérimentale du Cœur et des Muscles [U 1046] [PhyMedExp]
dc.contributor.authorSICARD, Pierre
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorDENEY, Antoine
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
hal.structure.identifierCHU Bordeaux
dc.contributor.authorCOUFFINHAL, Thierry
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
hal.structure.identifierCentre Hospitalier Universitaire de Toulouse [CHU Toulouse]
dc.contributor.authorSÉNARD, Jean-Michel
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorGALÉS, Céline
dc.date.accessioned2022-03-31T07:37:29Z
dc.date.available2022-03-31T07:37:29Z
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/136576
dc.description.abstractEnAbstract RATIONALE In addition to its typical rod-shape, the mammalian adult cardiomyocyte (CM) harbors a unique lateral membrane surface architecture with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) the role of which is still unknown. OBJECTIVE To investigate the development and functional role of CM crests during the postnatal period. METHODS AND RESULTS Electron/confocal microscopy and western-blot of left ventricular tissues from rat hearts indicated a late CM surface crest maturation, between postnatal day 20 (P20) and P60, as shown by substantial SSM swelling and increased claudin-5 cell surface expression. The P20-P60 postnatal stage also correlates with an ultimate maturation of the T-Tubules and the intercalated disk. At the cellular level, we identified an atypical CM hypertrophy characterized by an increase in long- and short-axes without myofibril addition and with sarcomere lateral stretching, indicative of lateral stretch-based CM hypertrophy. We confirmed the P20-P60 hypertrophy at the organ level by echocardiography but also demonstrated a transcriptomic program after P20 targeting all the cardiac cell populations. At the functional level, using Doppler echocardiography, we found that the P20-P60 period is specifically dedicated to the improvement of relaxation. Mechanistically, using CM-specific knock-out mice, we identified ephrin-B1 as a determinant of CM crest maturation after P20 controlling lateral CM stretch-hypertrophy and relaxation. Interestingly, while young adult Efnb1 CMspe−/− mice essentially show a relaxation impairment with exercise intolerance, they progressively switch toward heart failure with 100% KO mice dying after 13 months. CONCLUSIONS This study highlights a new late P20-P60 postnatal developmental stage of the heart in rodents during which the CM surface crests mature through an ephrin-B1-dependant mechanism and regulate the diastolic function. Moreover, we demonstrate for the first time that the CM crest architecture is cardioprotective.
dc.language.isoENen_US
dc.title.enCrest maturation at the cardiomyocyte surface contributes to a new late postnatal development stage that controls the diastolic function of the adult heart
dc.typeDocument de travail - Pré-publicationen_US
dc.identifier.doi10.1101/2022.02.11.480042en_US
dc.subject.halSciences du Vivant [q-bio]en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires (BMC) - UMR 1034en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.import.sourcehal
hal.identifierhal-03574569
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dc.rights.ccPas de Licence CCen_US
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