Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests
GUILBEAU-FRUGIER, Celine
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
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Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
GUILBEAU-FRUGIER, Celine
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
SEGUELAS, Marie-Helene
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
MONTAGNER, Alexandra
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
SICARD, Pierre
Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] [PhyMedExp]
Centre Hospitalier Régional Universitaire [Montpellier] [CHRU Montpellier]
Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] [PhyMedExp]
Centre Hospitalier Régional Universitaire [Montpellier] [CHRU Montpellier]
GALÉS, Celine
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
Centre Hospitalier Universitaire de Toulouse [CHU Toulouse]
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Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
Centre Hospitalier Universitaire de Toulouse [CHU Toulouse]
Idioma
EN
Article de revue
Este ítem está publicado en
eLife. 2023-01-17, vol. 12, p. e80904
Resumen en inglés
The rod-shaped adult cardiomyocyte (CM) harbors a unique architecture of its lateral surface with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) with unknown role. Here, we investigated the ...Leer más >
The rod-shaped adult cardiomyocyte (CM) harbors a unique architecture of its lateral surface with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) with unknown role. Here, we investigated the development and functional role of CM crests during the postnatal period. We found in rodents that CM crest maturation occurs late between postnatal day 20 (P20) and P60 through both SSM biogenesis, swelling and crest-crest lateral interactions between adjacent CM, promoting tissue compaction. At the functional level, we showed that the P20-P60 period is dedicated to the improvement of relaxation. Interestingly, crest maturation specifically contributes to an atypical CM hypertrophy of its short axis, without myofibril addition, but relying on CM lateral stretching. Mechanistically, using constitutive and conditional CM-specific knock-out mice, we identified ephrin-B1, a lateral membrane stabilizer, as a molecular determinant of P20-P60 crest maturation, governing both the CM lateral stretch and the diastolic function, thus highly suggesting a link between crest maturity and diastole. Remarkably, while young adult CM-specific Efnb1 KO mice essentially exhibit an impairment of the ventricular diastole with preserved ejection fraction and exercise intolerance, they progressively switch toward systolic heart failure with 100% KO mice dying after 13 months, indicative of a critical role of CM-ephrin-B1 in the adult heart function. This study highlights the molecular determinants and the biological implication of a new late P20-P60 postnatal developmental stage of the heart in rodents during which, in part, ephrin-B1 specifically regulates the maturation of the CM surface crests and of the diastolic function.< Leer menos
Palabras clave en inglés
cardiac hypertrophy
cardiac postnatal devleopment
cardiomyocyte architecture
cell biology
developmental biology
diatolic function
ephrin-B1
mouse
rat
subsarcolemmal mitochondria
cardiac hypertrophy
Centros de investigación