Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury

Acute kidney injury (AKI) is associated with an elevated risk of cardiovascular major events and mortality. The pathophysiological mechanisms underlying the complex cardiorenal network interaction remain unresolved. It is known that the presence of AKI and its evolution are significantly associated...

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Autores: González Lafuente, Laura, Navarro García, José Alberto, Valero Almazán, Ángela, Rodríguez Sánchez, Elena, Vázquez Sánchez, Sara, Mercado García, Elisa, Pineros, Patricia, Poveda, Jonay, Fernández Velasco, María, Kuro-O, Makoto, Ruilope, Luis Miguel, Ruiz Hurtado, Gema
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/718828
Acceso en línea:http://hdl.handle.net/10486/718828
https://dx.doi.org/10.3390/ijms24021322
Access Level:acceso abierto
Palabra clave:acute kidney injury
arrhythmia
calcium handling
cardiomyocyte
cardiorenal syndrome
klotho
Medicina
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spelling Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney InjuryGonzález Lafuente, LauraNavarro García, José AlbertoValero Almazán, ÁngelaRodríguez Sánchez, ElenaVázquez Sánchez, SaraMercado García, ElisaPineros, PatriciaPoveda, JonayFernández Velasco, MaríaKuro-O, MakotoRuilope, Luis MiguelRuiz Hurtado, Gemaacute kidney injuryarrhythmiacalcium handlingcardiomyocytecardiorenal syndromeklothoMedicinaAcute kidney injury (AKI) is associated with an elevated risk of cardiovascular major events and mortality. The pathophysiological mechanisms underlying the complex cardiorenal network interaction remain unresolved. It is known that the presence of AKI and its evolution are significantly associated with an alteration in the anti-aging factor klotho expression. However, it is unknown whether a klotho deficiency might aggravate cardiac damage after AKI. We examined intracellular calcium (Ca2+) handling in native ventricular isolated cardiomyocytes from wild-type (+/+) and heterozygous hypomorphic mice for the klotho gene (+/kl) in which an overdose of folic acid was administered to induce AKI. Twenty-four hours after AKI induction, cardiomyocyte contraction was decreased in mice with the partial deletion of klotho expression (heterozygous hypomorphic klotho named +/kl). This was accompanied by alterations in Ca2+ transients during systole and an impairment of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) function in +/kl mice after AKI induction. Moreover, Ca2+ spark frequency and the incidence of Ca2+ pro-arrhythmic events were greater in cardiomyocytes from heterozygous hypomorphic klotho compared to wild-type mice after AKI. A decrease in klotho expression plays a role in cardiorenal damage aggravating cardiac Ca2+ mishandling after an AKI, providing the basis for future targeted approaches directed to control klotho expression as novel therapeutic strategies to reduce the cardiac burden that affects AKI patientsThis work was mainly supported by projects from the Instituto de Salud Carlos III (ISCIII) [PI20/00763, CPII20/00022, FI18/00261, FI21/00212, FPU20/03005, CD19/00029] and co-funded by the European Union, and partially from the Education and Research Council of Madrid (PEJ-2021- AI/SAL-21426) by the Spanish Society of Nephrology SEN/SENEFRO FoundationMDPIDepartamento de FisiologíaFacultad de Medicina20232023-01-10research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/718828https://dx.doi.org/10.3390/ijms24021322reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7188282026-06-23T12:46:27Z
dc.title.none.fl_str_mv Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury
title Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury
spellingShingle Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury
González Lafuente, Laura
acute kidney injury
arrhythmia
calcium handling
cardiomyocyte
cardiorenal syndrome
klotho
Medicina
title_short Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury
title_full Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury
title_fullStr Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury
title_full_unstemmed Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury
title_sort Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury
dc.creator.none.fl_str_mv González Lafuente, Laura
Navarro García, José Alberto
Valero Almazán, Ángela
Rodríguez Sánchez, Elena
Vázquez Sánchez, Sara
Mercado García, Elisa
Pineros, Patricia
Poveda, Jonay
Fernández Velasco, María
Kuro-O, Makoto
Ruilope, Luis Miguel
Ruiz Hurtado, Gema
author González Lafuente, Laura
author_facet González Lafuente, Laura
Navarro García, José Alberto
Valero Almazán, Ángela
Rodríguez Sánchez, Elena
Vázquez Sánchez, Sara
Mercado García, Elisa
Pineros, Patricia
Poveda, Jonay
Fernández Velasco, María
Kuro-O, Makoto
Ruilope, Luis Miguel
Ruiz Hurtado, Gema
author_role author
author2 Navarro García, José Alberto
Valero Almazán, Ángela
Rodríguez Sánchez, Elena
Vázquez Sánchez, Sara
Mercado García, Elisa
Pineros, Patricia
Poveda, Jonay
Fernández Velasco, María
Kuro-O, Makoto
Ruilope, Luis Miguel
Ruiz Hurtado, Gema
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Fisiología
Facultad de Medicina
dc.subject.none.fl_str_mv acute kidney injury
arrhythmia
calcium handling
cardiomyocyte
cardiorenal syndrome
klotho
Medicina
topic acute kidney injury
arrhythmia
calcium handling
cardiomyocyte
cardiorenal syndrome
klotho
Medicina
description Acute kidney injury (AKI) is associated with an elevated risk of cardiovascular major events and mortality. The pathophysiological mechanisms underlying the complex cardiorenal network interaction remain unresolved. It is known that the presence of AKI and its evolution are significantly associated with an alteration in the anti-aging factor klotho expression. However, it is unknown whether a klotho deficiency might aggravate cardiac damage after AKI. We examined intracellular calcium (Ca2+) handling in native ventricular isolated cardiomyocytes from wild-type (+/+) and heterozygous hypomorphic mice for the klotho gene (+/kl) in which an overdose of folic acid was administered to induce AKI. Twenty-four hours after AKI induction, cardiomyocyte contraction was decreased in mice with the partial deletion of klotho expression (heterozygous hypomorphic klotho named +/kl). This was accompanied by alterations in Ca2+ transients during systole and an impairment of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) function in +/kl mice after AKI induction. Moreover, Ca2+ spark frequency and the incidence of Ca2+ pro-arrhythmic events were greater in cardiomyocytes from heterozygous hypomorphic klotho compared to wild-type mice after AKI. A decrease in klotho expression plays a role in cardiorenal damage aggravating cardiac Ca2+ mishandling after an AKI, providing the basis for future targeted approaches directed to control klotho expression as novel therapeutic strategies to reduce the cardiac burden that affects AKI patients
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-10
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/10486/718828
https://dx.doi.org/10.3390/ijms24021322
url http://hdl.handle.net/10486/718828
https://dx.doi.org/10.3390/ijms24021322
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
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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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