Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.

Heart failure (HF) is a complex syndrome characterized by cardiac dysfunction, Ca2+ mishandling, and chronic activation of the innate immune system. Reduced cardiac output in HF leads to compensatory mechanisms via activation of the adrenergic nervous system. In turn, chronic adrenergic overstimulat...

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Authors: Val Blasco, Almudena, Navarro García, José A., Tamayo, María, Garcia Miguel Piedras, María José, Prieto, Patricia, Delgado, Carmen, Ruiz Hurtado, Gema, Rozas Romero, Laura, Gil Fernández, Marta, Zaragoza Sánchez, Carlos, Boscá, Lisardo, Fernández Velasco, María
Format: article
Publication Date:2018
Country:España
Institution:Universidad Francisco de Vitoria
Repository:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Language:English
OAI Identifier:oai:ddfv.ufv.es:10641/1521
Online Access:http://hdl.handle.net/10641/1521
Access Level:Open access
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spelling Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.Val Blasco, AlmudenaNavarro García, José A.Tamayo, MaríaGarcia Miguel Piedras, María JoséPrieto, PatriciaDelgado, CarmenRuiz Hurtado, GemaRozas Romero, LauraGil Fernández, MartaZaragoza Sánchez, CarlosBoscá, LisardoFernández Velasco, MaríaHeart failure (HF) is a complex syndrome characterized by cardiac dysfunction, Ca2+ mishandling, and chronic activation of the innate immune system. Reduced cardiac output in HF leads to compensatory mechanisms via activation of the adrenergic nervous system. In turn, chronic adrenergic overstimulation induces pro-arrhythmic events, increasing the rate of sudden death in failing patients. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is an innate immune modulator that plays a key role in HF progression. NOD1 deficiency in mice prevents Ca2+ mishandling in HF under basal conditions, but its role during β-adrenergic stimulation remains unknown. Here, we evaluated whether NOD1 regulates the β-adrenergic modulation of Ca2+ signaling in HF. Ca2+ dynamics were examined before and after isoproterenol perfusion in cardiomyocytes isolated from healthy and from post-myocardial infarction (PMI) wild-type (WT) and Nod1-/- mice. Isoproterenol administration induced similar effects on intracellular [Ca2+]i transients, cell contraction, and sarcoplasmic reticulum (SR)-Ca2+ load in healthy WT and Nod1-/- cells. However, compared with WT-PMI cells, isoproterenol exposure induced a significant increase in the [Ca2+]i transients and cell contraction parameters in Nod1-/--PMI cells, which mainly due to an increase in SR-Ca2+ load. NOD1 deficiency also prevented the increase in diastolic Ca2+ leak (Ca2+ waves) induced by isoproterenol in PMI cells. mRNA levels of β1 and β2 adrenergic receptors were significantly higher in Nod1-/--PMI hearts vs WT-PMI hearts. Healthy cardiomyocytes pre-treated with the selective agonist of NOD1, iE-DAP, and perfused with isoproterenol showed diminished [Ca2+]i transients amplitude, cell contraction, and SR-Ca2+ load compared with vehicle-treated cells. iE-DAP-treated cells also presented increased diastolic Ca2+ leak under β-adrenergic stimulation. The selectivity of iE-DAP on Ca2+ handling was validated by pre-treatment with the inactive analog of NOD1, iE-Lys. Overall, our data establish that NOD1 deficiency improves the β-adrenergic modulation of Ca2+ handling in failing hearts.20182018-01-0120182018-01-01journal articlehttp://purl.org/coar/resource_type/c_6501SMURhttp://purl.org/coar/version/c_71e4c1898caa6e32info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10641/1521reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad Francisco de VitoriaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-SinDerivadas 3.0 Españahttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/15212026-06-11T12:44:57Z
dc.title.none.fl_str_mv Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.
title Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.
spellingShingle Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.
Val Blasco, Almudena
title_short Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.
title_full Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.
title_fullStr Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.
title_full_unstemmed Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.
title_sort Deficiency of NOD1 Improves the b-Adrenergic Modulation of Ca2C Handling in a Mouse Model of Heart Failure.
dc.creator.none.fl_str_mv Val Blasco, Almudena
Navarro García, José A.
Tamayo, María
Garcia Miguel Piedras, María José
Prieto, Patricia
Delgado, Carmen
Ruiz Hurtado, Gema
Rozas Romero, Laura
Gil Fernández, Marta
Zaragoza Sánchez, Carlos
Boscá, Lisardo
Fernández Velasco, María
author Val Blasco, Almudena
author_facet Val Blasco, Almudena
Navarro García, José A.
Tamayo, María
Garcia Miguel Piedras, María José
Prieto, Patricia
Delgado, Carmen
Ruiz Hurtado, Gema
Rozas Romero, Laura
Gil Fernández, Marta
Zaragoza Sánchez, Carlos
Boscá, Lisardo
Fernández Velasco, María
author_role author
author2 Navarro García, José A.
Tamayo, María
Garcia Miguel Piedras, María José
Prieto, Patricia
Delgado, Carmen
Ruiz Hurtado, Gema
Rozas Romero, Laura
Gil Fernández, Marta
Zaragoza Sánchez, Carlos
Boscá, Lisardo
Fernández Velasco, María
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
description Heart failure (HF) is a complex syndrome characterized by cardiac dysfunction, Ca2+ mishandling, and chronic activation of the innate immune system. Reduced cardiac output in HF leads to compensatory mechanisms via activation of the adrenergic nervous system. In turn, chronic adrenergic overstimulation induces pro-arrhythmic events, increasing the rate of sudden death in failing patients. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is an innate immune modulator that plays a key role in HF progression. NOD1 deficiency in mice prevents Ca2+ mishandling in HF under basal conditions, but its role during β-adrenergic stimulation remains unknown. Here, we evaluated whether NOD1 regulates the β-adrenergic modulation of Ca2+ signaling in HF. Ca2+ dynamics were examined before and after isoproterenol perfusion in cardiomyocytes isolated from healthy and from post-myocardial infarction (PMI) wild-type (WT) and Nod1-/- mice. Isoproterenol administration induced similar effects on intracellular [Ca2+]i transients, cell contraction, and sarcoplasmic reticulum (SR)-Ca2+ load in healthy WT and Nod1-/- cells. However, compared with WT-PMI cells, isoproterenol exposure induced a significant increase in the [Ca2+]i transients and cell contraction parameters in Nod1-/--PMI cells, which mainly due to an increase in SR-Ca2+ load. NOD1 deficiency also prevented the increase in diastolic Ca2+ leak (Ca2+ waves) induced by isoproterenol in PMI cells. mRNA levels of β1 and β2 adrenergic receptors were significantly higher in Nod1-/--PMI hearts vs WT-PMI hearts. Healthy cardiomyocytes pre-treated with the selective agonist of NOD1, iE-DAP, and perfused with isoproterenol showed diminished [Ca2+]i transients amplitude, cell contraction, and SR-Ca2+ load compared with vehicle-treated cells. iE-DAP-treated cells also presented increased diastolic Ca2+ leak under β-adrenergic stimulation. The selectivity of iE-DAP on Ca2+ handling was validated by pre-treatment with the inactive analog of NOD1, iE-Lys. Overall, our data establish that NOD1 deficiency improves the β-adrenergic modulation of Ca2+ handling in failing hearts.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
SMUR
http://purl.org/coar/version/c_71e4c1898caa6e32
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10641/1521
url http://hdl.handle.net/10641/1521
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
Atribución-NoComercial-SinDerivadas 3.0 España
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
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
Atribución-NoComercial-SinDerivadas 3.0 España
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
instname:Universidad Francisco de Vitoria
instname_str Universidad Francisco de Vitoria
reponame_str DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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