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Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests

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 fo...

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Autores principales: Karsenty, Clement, Guilbeau-Frugier, Celine, Genet, Gaël, Seguelas, Marie-Helene, Alzieu, Philippe, Cazorla, Olivier, Montagner, Alexandra, Blum, Yuna, Dubroca, Caroline, Maupoint, Julile, Tramunt, Blandine, Cauquil, Marie, Sulpice, Thierry, Richard, Sylvain, Arcucci, Silvia, Flores-Flores, Remy, Pataluch, Nicolas, Montoriol, Romain, Sicard, Pierre, Deney, Antoine, Couffinhal, Thierry, Senard, Jean-Michel, Galés, Celine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844986/
https://www.ncbi.nlm.nih.gov/pubmed/36649053
http://dx.doi.org/10.7554/eLife.80904
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author Karsenty, Clement
Guilbeau-Frugier, Celine
Genet, Gaël
Seguelas, Marie-Helene
Alzieu, Philippe
Cazorla, Olivier
Montagner, Alexandra
Blum, Yuna
Dubroca, Caroline
Maupoint, Julile
Tramunt, Blandine
Cauquil, Marie
Sulpice, Thierry
Richard, Sylvain
Arcucci, Silvia
Flores-Flores, Remy
Pataluch, Nicolas
Montoriol, Romain
Sicard, Pierre
Deney, Antoine
Couffinhal, Thierry
Senard, Jean-Michel
Galés, Celine
author_facet Karsenty, Clement
Guilbeau-Frugier, Celine
Genet, Gaël
Seguelas, Marie-Helene
Alzieu, Philippe
Cazorla, Olivier
Montagner, Alexandra
Blum, Yuna
Dubroca, Caroline
Maupoint, Julile
Tramunt, Blandine
Cauquil, Marie
Sulpice, Thierry
Richard, Sylvain
Arcucci, Silvia
Flores-Flores, Remy
Pataluch, Nicolas
Montoriol, Romain
Sicard, Pierre
Deney, Antoine
Couffinhal, Thierry
Senard, Jean-Michel
Galés, Celine
author_sort Karsenty, Clement
collection PubMed
description 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.
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spelling pubmed-98449862023-01-18 Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests Karsenty, Clement Guilbeau-Frugier, Celine Genet, Gaël Seguelas, Marie-Helene Alzieu, Philippe Cazorla, Olivier Montagner, Alexandra Blum, Yuna Dubroca, Caroline Maupoint, Julile Tramunt, Blandine Cauquil, Marie Sulpice, Thierry Richard, Sylvain Arcucci, Silvia Flores-Flores, Remy Pataluch, Nicolas Montoriol, Romain Sicard, Pierre Deney, Antoine Couffinhal, Thierry Senard, Jean-Michel Galés, Celine eLife Cell Biology 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. eLife Sciences Publications, Ltd 2023-01-17 /pmc/articles/PMC9844986/ /pubmed/36649053 http://dx.doi.org/10.7554/eLife.80904 Text en © 2023, Karsenty et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Karsenty, Clement
Guilbeau-Frugier, Celine
Genet, Gaël
Seguelas, Marie-Helene
Alzieu, Philippe
Cazorla, Olivier
Montagner, Alexandra
Blum, Yuna
Dubroca, Caroline
Maupoint, Julile
Tramunt, Blandine
Cauquil, Marie
Sulpice, Thierry
Richard, Sylvain
Arcucci, Silvia
Flores-Flores, Remy
Pataluch, Nicolas
Montoriol, Romain
Sicard, Pierre
Deney, Antoine
Couffinhal, Thierry
Senard, Jean-Michel
Galés, Celine
Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests
title Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests
title_full Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests
title_fullStr Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests
title_full_unstemmed Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests
title_short Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests
title_sort ephrin-b1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844986/
https://www.ncbi.nlm.nih.gov/pubmed/36649053
http://dx.doi.org/10.7554/eLife.80904
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