Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality

Autores
Actis Dato, Virginia; Paz, Maria Constanza; Rey, Federico E.; Sanchez, Maria Cecilia; Llorente Cortés, Vicenta; Chiabrando, Gustavo Alberto; Ceschin, Danilo Guillermo
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cardiovascular disease (CVD) is a multisystemic and multicellular pathology that is generally associated with high levels of atherogenic lipoproteins in circulation. These lipoproteins tend to be retained and modifed, for example, aggregated low-density lipoprotein (aggLDL), in the extracellular matrix of diferent tissues, such as the vascular wall and heart. The uptake of aggLDL generates a signifcant increase in cholesteryl ester (CE) in these tissues. We previously found that the accumulation of CE generates alterations in the insulin response in the heart. Although the insulin response is mainly associated with the uptake and metabolism of glucose, other studies have shown that insulin would fulfll functions in this tissue, such as regulating the calcium cycle and cardiac contractility. Here, we found that aggLDL induced-lipid accumulation altered the gene expression profle involved in processes essential for cardiac functionality, including insulin response and glucose uptake (Insr, Ins1, Pik3ip1, Slc2a4 gene expression), calcium cycle (Cacna1s and Gjc2 gene expression) and calcium-dependent cardiac contractility (Myh3), and cholesterol efux (Abca1), in HL-1 cardiomyocytes. These observations were recapitulated using an in vivo model of hypercholesterolemic ApoE-KO mice. Altogether, these results may explain the deleterious efect of lipid accumulation in the myocardium, with important implications for lipid-overloaded associated CVD, including impaired insulin response, disrupted lipid metabolism, altered cardiac structure, and increased susceptibility to cardiovascular events.
Fil: Actis Dato, Virginia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Paz, Maria Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Rey, Federico E.. University of Wisconsin; Estados Unidos
Fil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Llorente Cortés, Vicenta. University of Wisconsin; Estados Unidos
Fil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ceschin, Danilo Guillermo. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Materia
colesterol
LDL
cardiomiocytes
gene expression
LDL
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/227010
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/227010
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network_name_str CONICET Digital (CONICET)
spelling Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionalityActis Dato, VirginiaPaz, Maria ConstanzaRey, Federico E.Sanchez, Maria CeciliaLlorente Cortés, VicentaChiabrando, Gustavo AlbertoCeschin, Danilo GuillermocolesterolLDLcardiomiocytesgene expressionLDLhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Cardiovascular disease (CVD) is a multisystemic and multicellular pathology that is generally associated with high levels of atherogenic lipoproteins in circulation. These lipoproteins tend to be retained and modifed, for example, aggregated low-density lipoprotein (aggLDL), in the extracellular matrix of diferent tissues, such as the vascular wall and heart. The uptake of aggLDL generates a signifcant increase in cholesteryl ester (CE) in these tissues. We previously found that the accumulation of CE generates alterations in the insulin response in the heart. Although the insulin response is mainly associated with the uptake and metabolism of glucose, other studies have shown that insulin would fulfll functions in this tissue, such as regulating the calcium cycle and cardiac contractility. Here, we found that aggLDL induced-lipid accumulation altered the gene expression profle involved in processes essential for cardiac functionality, including insulin response and glucose uptake (Insr, Ins1, Pik3ip1, Slc2a4 gene expression), calcium cycle (Cacna1s and Gjc2 gene expression) and calcium-dependent cardiac contractility (Myh3), and cholesterol efux (Abca1), in HL-1 cardiomyocytes. These observations were recapitulated using an in vivo model of hypercholesterolemic ApoE-KO mice. Altogether, these results may explain the deleterious efect of lipid accumulation in the myocardium, with important implications for lipid-overloaded associated CVD, including impaired insulin response, disrupted lipid metabolism, altered cardiac structure, and increased susceptibility to cardiovascular events.Fil: Actis Dato, Virginia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Paz, Maria Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Rey, Federico E.. University of Wisconsin; Estados UnidosFil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Llorente Cortés, Vicenta. University of Wisconsin; Estados UnidosFil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ceschin, Danilo Guillermo. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaNature Research2023-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227010Actis Dato, Virginia; Paz, Maria Constanza; Rey, Federico E.; Sanchez, Maria Cecilia; Llorente Cortés, Vicenta; et al.; Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality; Nature Research; Scientific Reports; 13; 1; 12-2023; 1-112045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-023-35951-6info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-023-35951-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:08:39Zoai:ri.conicet.gov.ar:11336/227010instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:08:39.484CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality
title Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality
spellingShingle Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality
Actis Dato, Virginia
colesterol
LDL
cardiomiocytes
gene expression
LDL
title_short Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality
title_full Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality
title_fullStr Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality
title_full_unstemmed Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality
title_sort Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality
dc.creator.none.fl_str_mv Actis Dato, Virginia
Paz, Maria Constanza
Rey, Federico E.
Sanchez, Maria Cecilia
Llorente Cortés, Vicenta
Chiabrando, Gustavo Alberto
Ceschin, Danilo Guillermo
author Actis Dato, Virginia
author_facet Actis Dato, Virginia
Paz, Maria Constanza
Rey, Federico E.
Sanchez, Maria Cecilia
Llorente Cortés, Vicenta
Chiabrando, Gustavo Alberto
Ceschin, Danilo Guillermo
author_role author
author2 Paz, Maria Constanza
Rey, Federico E.
Sanchez, Maria Cecilia
Llorente Cortés, Vicenta
Chiabrando, Gustavo Alberto
Ceschin, Danilo Guillermo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv colesterol
LDL
cardiomiocytes
gene expression
LDL
topic colesterol
LDL
cardiomiocytes
gene expression
LDL
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cardiovascular disease (CVD) is a multisystemic and multicellular pathology that is generally associated with high levels of atherogenic lipoproteins in circulation. These lipoproteins tend to be retained and modifed, for example, aggregated low-density lipoprotein (aggLDL), in the extracellular matrix of diferent tissues, such as the vascular wall and heart. The uptake of aggLDL generates a signifcant increase in cholesteryl ester (CE) in these tissues. We previously found that the accumulation of CE generates alterations in the insulin response in the heart. Although the insulin response is mainly associated with the uptake and metabolism of glucose, other studies have shown that insulin would fulfll functions in this tissue, such as regulating the calcium cycle and cardiac contractility. Here, we found that aggLDL induced-lipid accumulation altered the gene expression profle involved in processes essential for cardiac functionality, including insulin response and glucose uptake (Insr, Ins1, Pik3ip1, Slc2a4 gene expression), calcium cycle (Cacna1s and Gjc2 gene expression) and calcium-dependent cardiac contractility (Myh3), and cholesterol efux (Abca1), in HL-1 cardiomyocytes. These observations were recapitulated using an in vivo model of hypercholesterolemic ApoE-KO mice. Altogether, these results may explain the deleterious efect of lipid accumulation in the myocardium, with important implications for lipid-overloaded associated CVD, including impaired insulin response, disrupted lipid metabolism, altered cardiac structure, and increased susceptibility to cardiovascular events.
Fil: Actis Dato, Virginia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Paz, Maria Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Rey, Federico E.. University of Wisconsin; Estados Unidos
Fil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Llorente Cortés, Vicenta. University of Wisconsin; Estados Unidos
Fil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ceschin, Danilo Guillermo. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
description Cardiovascular disease (CVD) is a multisystemic and multicellular pathology that is generally associated with high levels of atherogenic lipoproteins in circulation. These lipoproteins tend to be retained and modifed, for example, aggregated low-density lipoprotein (aggLDL), in the extracellular matrix of diferent tissues, such as the vascular wall and heart. The uptake of aggLDL generates a signifcant increase in cholesteryl ester (CE) in these tissues. We previously found that the accumulation of CE generates alterations in the insulin response in the heart. Although the insulin response is mainly associated with the uptake and metabolism of glucose, other studies have shown that insulin would fulfll functions in this tissue, such as regulating the calcium cycle and cardiac contractility. Here, we found that aggLDL induced-lipid accumulation altered the gene expression profle involved in processes essential for cardiac functionality, including insulin response and glucose uptake (Insr, Ins1, Pik3ip1, Slc2a4 gene expression), calcium cycle (Cacna1s and Gjc2 gene expression) and calcium-dependent cardiac contractility (Myh3), and cholesterol efux (Abca1), in HL-1 cardiomyocytes. These observations were recapitulated using an in vivo model of hypercholesterolemic ApoE-KO mice. Altogether, these results may explain the deleterious efect of lipid accumulation in the myocardium, with important implications for lipid-overloaded associated CVD, including impaired insulin response, disrupted lipid metabolism, altered cardiac structure, and increased susceptibility to cardiovascular events.
publishDate 2023
dc.date.none.fl_str_mv 2023-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/227010
Actis Dato, Virginia; Paz, Maria Constanza; Rey, Federico E.; Sanchez, Maria Cecilia; Llorente Cortés, Vicenta; et al.; Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality; Nature Research; Scientific Reports; 13; 1; 12-2023; 1-11
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227010
identifier_str_mv Actis Dato, Virginia; Paz, Maria Constanza; Rey, Federico E.; Sanchez, Maria Cecilia; Llorente Cortés, Vicenta; et al.; Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality; Nature Research; Scientific Reports; 13; 1; 12-2023; 1-11
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-023-35951-6
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-023-35951-6
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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