Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathy

Propionic acidemia (PA) disorder shows major involvement of the heart, among other alterations. A significant number of PA patients develop cardiac complications, and available evidence suggests that this cardiac dysfunction is driven mainly by the accumulation of toxic metabolites. To contribute to...

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Detalhes bibliográficos
Autores: Álvarez, Mar, Ruiz-Sala, Pedro, Estébanez Pérez, Belén, Ruiz Desviat, Lourdes, Richard Rodríguez, Eva María
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/706830
Acesso em linha:http://hdl.handle.net/10486/706830
https://dx.doi.org/10.3390/ijms24032182
Access Level:acceso abierto
Palavra-chave:iPSC
PCCB
iPSC-Derived Cardiomyocytes
Propionic Acidemia
MicroRNAs
Biología y Biomedicina / Biología
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spelling Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathyÁlvarez, MarRuiz-Sala, PedroEstébanez Pérez, BelénRuiz Desviat, LourdesRichard Rodríguez, Eva MaríaiPSCPCCBiPSC-Derived CardiomyocytesPropionic AcidemiaMicroRNAsBiología y Biomedicina / BiologíaPropionic acidemia (PA) disorder shows major involvement of the heart, among other alterations. A significant number of PA patients develop cardiac complications, and available evidence suggests that this cardiac dysfunction is driven mainly by the accumulation of toxic metabolites. To contribute to the elucidation of the mechanistic basis underlying this dysfunction, we have successfully generated cardiomyocytes through the differentiation of induced pluripotent stem cells (iPSCs) from a PCCB patient and its isogenic control. In this human cellular model, we aimed to examine microRNAs (miRNAs) profiles and analyze several cellular pathways to determine miRNAs activity patterns associated with PA cardiac phenotypes. We have identified a series of upregulated cardiac-enriched miRNAs and alterations in some of their regulated signaling pathways, including an increase in the expression of cardiac damage markers and cardiac channels, an increase in oxidative stress, a decrease in mitochondrial respiration and autophagy; and lipid accumulation. Our findings indicate that miRNA activity patterns from PA iPSC-derived cardiomyocytes are biologically informative and advance the understanding of the molecular mechanisms of this rare disease, providing a basis for identifying new therapeutic targets for intervention strategiesMDPIDepartamento de BiologíaDepartamento de Biología MolecularFacultad de Ciencias20232023-01-22research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/706830https://dx.doi.org/10.3390/ijms24032182reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7068302026-06-23T12:46:27Z
dc.title.none.fl_str_mv Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathy
title Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathy
spellingShingle Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathy
Álvarez, Mar
iPSC
PCCB
iPSC-Derived Cardiomyocytes
Propionic Acidemia
MicroRNAs
Biología y Biomedicina / Biología
title_short Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathy
title_full Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathy
title_fullStr Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathy
title_full_unstemmed Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathy
title_sort Dysregulated cell homeostasis and miRNAs in human iPSC-derived cardiomyocytes from a propionic acidemia patient with cardiomyopathy
dc.creator.none.fl_str_mv Álvarez, Mar
Ruiz-Sala, Pedro
Estébanez Pérez, Belén
Ruiz Desviat, Lourdes
Richard Rodríguez, Eva María
author Álvarez, Mar
author_facet Álvarez, Mar
Ruiz-Sala, Pedro
Estébanez Pérez, Belén
Ruiz Desviat, Lourdes
Richard Rodríguez, Eva María
author_role author
author2 Ruiz-Sala, Pedro
Estébanez Pérez, Belén
Ruiz Desviat, Lourdes
Richard Rodríguez, Eva María
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología
Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv iPSC
PCCB
iPSC-Derived Cardiomyocytes
Propionic Acidemia
MicroRNAs
Biología y Biomedicina / Biología
topic iPSC
PCCB
iPSC-Derived Cardiomyocytes
Propionic Acidemia
MicroRNAs
Biología y Biomedicina / Biología
description Propionic acidemia (PA) disorder shows major involvement of the heart, among other alterations. A significant number of PA patients develop cardiac complications, and available evidence suggests that this cardiac dysfunction is driven mainly by the accumulation of toxic metabolites. To contribute to the elucidation of the mechanistic basis underlying this dysfunction, we have successfully generated cardiomyocytes through the differentiation of induced pluripotent stem cells (iPSCs) from a PCCB patient and its isogenic control. In this human cellular model, we aimed to examine microRNAs (miRNAs) profiles and analyze several cellular pathways to determine miRNAs activity patterns associated with PA cardiac phenotypes. We have identified a series of upregulated cardiac-enriched miRNAs and alterations in some of their regulated signaling pathways, including an increase in the expression of cardiac damage markers and cardiac channels, an increase in oxidative stress, a decrease in mitochondrial respiration and autophagy; and lipid accumulation. Our findings indicate that miRNA activity patterns from PA iPSC-derived cardiomyocytes are biologically informative and advance the understanding of the molecular mechanisms of this rare disease, providing a basis for identifying new therapeutic targets for intervention strategies
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-22
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/706830
https://dx.doi.org/10.3390/ijms24032182
url http://hdl.handle.net/10486/706830
https://dx.doi.org/10.3390/ijms24032182
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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