Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arr...

Autores
Agorrody, Guillermo; Peclat, Thais R.; Peluso, Gonzalo; Gonano, Luis Alberto; Santos, Leonardo; van Schooten, Wim; Chini, Claudia C. S.; Escande, Carlos; Chini, Eduardo N.; Contreras, Paola
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
CD38 enzymatic activity regulates NAD+ and cADPR levels in mammalian tissues, and therefore has a prominent role in cellular metabolism and calcium homeostasis. Consequently, it is reasonable to hypothesize about its involvement in cardiovascular physiology as well as in heart related pathological conditions. Aim: To investigate the role of CD38 in cardiovascular performance, and its involvement in cardiac electrophysiology and calcium-handling. Methods and results: When submitted to a treadmill exhaustion test, a way of evaluating cardiovascular performance, adult male CD38KO mice showed better exercise capacity. This benefit was also obtained in genetically modified mice with catalytically inactive (CI) CD38 and in WT mice treated with antibody 68 (Ab68) which blocks CD38 activity. Hearts from these 3 groups (CD38KO, CD38CI and Ab68) showed increased NAD+ levels. When CD38KO mice were treated with FK866 which inhibits NAD+ biosynthesis, exercise capacity as well as NAD+ in heart tissue decreased to WT levels. Electrocardiograms of conscious unrestrained CD38KO and CD38CI mice showed lower basal heart rates and higher heart rate variability than WT mice. Although inactivation of CD38 in mice resulted in increased SERCA2a expression in the heart, the frequency of spontaneous calcium release from the sarcoplasmic reticulum under stressful conditions (high extracellular calcium concentration) was lower in CD38KO ventricular myocytes. When mice were challenged with caffeine-epinephrine, CD38KO mice had a lower incidence of bidirectional ventricular tachycardia when compared to WT ones. Conclusion: CD38 inhibition improves exercise performance by regulating NAD+ homeostasis. CD38 is involved in cardiovascular function since its genetic ablation decreases basal heart rate, increases heart rate variability and alters calcium handling in a way that protects mice from developing catecholamine induced ventricular arrhythmias.
Fil: Agorrody, Guillermo. Universidad de la Republica. Facultad de Medicina; Uruguay
Fil: Peclat, Thais R.. Mayo Clinic College Of Medicine; Estados Unidos
Fil: Peluso, Gonzalo. Universidad de la Republica. Facultad de Medicina; Uruguay
Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Santos, Leonardo. Instituto Pasteur de Montevideo; Uruguay
Fil: van Schooten, Wim. Teneobio; Estados Unidos
Fil: Chini, Claudia C. S.. Mayo Clinic College Of Medicine; Estados Unidos
Fil: Escande, Carlos. Instituto Pasteur de Montevideo; Uruguay
Fil: Chini, Eduardo N.. Mayo Clinic College Of Medicine; Estados Unidos
Fil: Contreras, Paola. Universidad de la Republica. Facultad de Medicina; Uruguay
Materia
ACTION POTENTIAL
ARRHYTHMIA
CALCIUM
CD38
EXERCISE CAPACITY
HEART
NAD+
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:11336/212479
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/212479
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmiasAgorrody, GuillermoPeclat, Thais R.Peluso, GonzaloGonano, Luis AlbertoSantos, Leonardovan Schooten, WimChini, Claudia C. S.Escande, CarlosChini, Eduardo N.Contreras, PaolaACTION POTENTIALARRHYTHMIACALCIUMCD38EXERCISE CAPACITYHEARTNAD+https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3CD38 enzymatic activity regulates NAD+ and cADPR levels in mammalian tissues, and therefore has a prominent role in cellular metabolism and calcium homeostasis. Consequently, it is reasonable to hypothesize about its involvement in cardiovascular physiology as well as in heart related pathological conditions. Aim: To investigate the role of CD38 in cardiovascular performance, and its involvement in cardiac electrophysiology and calcium-handling. Methods and results: When submitted to a treadmill exhaustion test, a way of evaluating cardiovascular performance, adult male CD38KO mice showed better exercise capacity. This benefit was also obtained in genetically modified mice with catalytically inactive (CI) CD38 and in WT mice treated with antibody 68 (Ab68) which blocks CD38 activity. Hearts from these 3 groups (CD38KO, CD38CI and Ab68) showed increased NAD+ levels. When CD38KO mice were treated with FK866 which inhibits NAD+ biosynthesis, exercise capacity as well as NAD+ in heart tissue decreased to WT levels. Electrocardiograms of conscious unrestrained CD38KO and CD38CI mice showed lower basal heart rates and higher heart rate variability than WT mice. Although inactivation of CD38 in mice resulted in increased SERCA2a expression in the heart, the frequency of spontaneous calcium release from the sarcoplasmic reticulum under stressful conditions (high extracellular calcium concentration) was lower in CD38KO ventricular myocytes. When mice were challenged with caffeine-epinephrine, CD38KO mice had a lower incidence of bidirectional ventricular tachycardia when compared to WT ones. Conclusion: CD38 inhibition improves exercise performance by regulating NAD+ homeostasis. CD38 is involved in cardiovascular function since its genetic ablation decreases basal heart rate, increases heart rate variability and alters calcium handling in a way that protects mice from developing catecholamine induced ventricular arrhythmias.Fil: Agorrody, Guillermo. Universidad de la Republica. Facultad de Medicina; UruguayFil: Peclat, Thais R.. Mayo Clinic College Of Medicine; Estados UnidosFil: Peluso, Gonzalo. Universidad de la Republica. Facultad de Medicina; UruguayFil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Santos, Leonardo. Instituto Pasteur de Montevideo; UruguayFil: van Schooten, Wim. Teneobio; Estados UnidosFil: Chini, Claudia C. S.. Mayo Clinic College Of Medicine; Estados UnidosFil: Escande, Carlos. Instituto Pasteur de Montevideo; UruguayFil: Chini, Eduardo N.. Mayo Clinic College Of Medicine; Estados UnidosFil: Contreras, Paola. Universidad de la Republica. Facultad de Medicina; UruguayAcademic Press Ltd - Elsevier Science Ltd2022-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/212479Agorrody, Guillermo; Peclat, Thais R.; Peluso, Gonzalo; Gonano, Luis Alberto; Santos, Leonardo; et al.; Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 166; 5-2022; 11-220022-2828CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0022282822000190info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yjmcc.2022.01.008info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:39:39Zoai:ri.conicet.gov.ar:11336/212479instacron: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:34982025-09-29 10:39:40.187CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias
title Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias
spellingShingle Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias
Agorrody, Guillermo
ACTION POTENTIAL
ARRHYTHMIA
CALCIUM
CD38
EXERCISE CAPACITY
HEART
NAD+
title_short Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias
title_full Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias
title_fullStr Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias
title_full_unstemmed Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias
title_sort Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias
dc.creator.none.fl_str_mv Agorrody, Guillermo
Peclat, Thais R.
Peluso, Gonzalo
Gonano, Luis Alberto
Santos, Leonardo
van Schooten, Wim
Chini, Claudia C. S.
Escande, Carlos
Chini, Eduardo N.
Contreras, Paola
author Agorrody, Guillermo
author_facet Agorrody, Guillermo
Peclat, Thais R.
Peluso, Gonzalo
Gonano, Luis Alberto
Santos, Leonardo
van Schooten, Wim
Chini, Claudia C. S.
Escande, Carlos
Chini, Eduardo N.
Contreras, Paola
author_role author
author2 Peclat, Thais R.
Peluso, Gonzalo
Gonano, Luis Alberto
Santos, Leonardo
van Schooten, Wim
Chini, Claudia C. S.
Escande, Carlos
Chini, Eduardo N.
Contreras, Paola
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACTION POTENTIAL
ARRHYTHMIA
CALCIUM
CD38
EXERCISE CAPACITY
HEART
NAD+
topic ACTION POTENTIAL
ARRHYTHMIA
CALCIUM
CD38
EXERCISE CAPACITY
HEART
NAD+
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv CD38 enzymatic activity regulates NAD+ and cADPR levels in mammalian tissues, and therefore has a prominent role in cellular metabolism and calcium homeostasis. Consequently, it is reasonable to hypothesize about its involvement in cardiovascular physiology as well as in heart related pathological conditions. Aim: To investigate the role of CD38 in cardiovascular performance, and its involvement in cardiac electrophysiology and calcium-handling. Methods and results: When submitted to a treadmill exhaustion test, a way of evaluating cardiovascular performance, adult male CD38KO mice showed better exercise capacity. This benefit was also obtained in genetically modified mice with catalytically inactive (CI) CD38 and in WT mice treated with antibody 68 (Ab68) which blocks CD38 activity. Hearts from these 3 groups (CD38KO, CD38CI and Ab68) showed increased NAD+ levels. When CD38KO mice were treated with FK866 which inhibits NAD+ biosynthesis, exercise capacity as well as NAD+ in heart tissue decreased to WT levels. Electrocardiograms of conscious unrestrained CD38KO and CD38CI mice showed lower basal heart rates and higher heart rate variability than WT mice. Although inactivation of CD38 in mice resulted in increased SERCA2a expression in the heart, the frequency of spontaneous calcium release from the sarcoplasmic reticulum under stressful conditions (high extracellular calcium concentration) was lower in CD38KO ventricular myocytes. When mice were challenged with caffeine-epinephrine, CD38KO mice had a lower incidence of bidirectional ventricular tachycardia when compared to WT ones. Conclusion: CD38 inhibition improves exercise performance by regulating NAD+ homeostasis. CD38 is involved in cardiovascular function since its genetic ablation decreases basal heart rate, increases heart rate variability and alters calcium handling in a way that protects mice from developing catecholamine induced ventricular arrhythmias.
Fil: Agorrody, Guillermo. Universidad de la Republica. Facultad de Medicina; Uruguay
Fil: Peclat, Thais R.. Mayo Clinic College Of Medicine; Estados Unidos
Fil: Peluso, Gonzalo. Universidad de la Republica. Facultad de Medicina; Uruguay
Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Santos, Leonardo. Instituto Pasteur de Montevideo; Uruguay
Fil: van Schooten, Wim. Teneobio; Estados Unidos
Fil: Chini, Claudia C. S.. Mayo Clinic College Of Medicine; Estados Unidos
Fil: Escande, Carlos. Instituto Pasteur de Montevideo; Uruguay
Fil: Chini, Eduardo N.. Mayo Clinic College Of Medicine; Estados Unidos
Fil: Contreras, Paola. Universidad de la Republica. Facultad de Medicina; Uruguay
description CD38 enzymatic activity regulates NAD+ and cADPR levels in mammalian tissues, and therefore has a prominent role in cellular metabolism and calcium homeostasis. Consequently, it is reasonable to hypothesize about its involvement in cardiovascular physiology as well as in heart related pathological conditions. Aim: To investigate the role of CD38 in cardiovascular performance, and its involvement in cardiac electrophysiology and calcium-handling. Methods and results: When submitted to a treadmill exhaustion test, a way of evaluating cardiovascular performance, adult male CD38KO mice showed better exercise capacity. This benefit was also obtained in genetically modified mice with catalytically inactive (CI) CD38 and in WT mice treated with antibody 68 (Ab68) which blocks CD38 activity. Hearts from these 3 groups (CD38KO, CD38CI and Ab68) showed increased NAD+ levels. When CD38KO mice were treated with FK866 which inhibits NAD+ biosynthesis, exercise capacity as well as NAD+ in heart tissue decreased to WT levels. Electrocardiograms of conscious unrestrained CD38KO and CD38CI mice showed lower basal heart rates and higher heart rate variability than WT mice. Although inactivation of CD38 in mice resulted in increased SERCA2a expression in the heart, the frequency of spontaneous calcium release from the sarcoplasmic reticulum under stressful conditions (high extracellular calcium concentration) was lower in CD38KO ventricular myocytes. When mice were challenged with caffeine-epinephrine, CD38KO mice had a lower incidence of bidirectional ventricular tachycardia when compared to WT ones. Conclusion: CD38 inhibition improves exercise performance by regulating NAD+ homeostasis. CD38 is involved in cardiovascular function since its genetic ablation decreases basal heart rate, increases heart rate variability and alters calcium handling in a way that protects mice from developing catecholamine induced ventricular arrhythmias.
publishDate 2022
dc.date.none.fl_str_mv 2022-05
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/11336/212479
Agorrody, Guillermo; Peclat, Thais R.; Peluso, Gonzalo; Gonano, Luis Alberto; Santos, Leonardo; et al.; Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 166; 5-2022; 11-22
0022-2828
CONICET Digital
CONICET
url http://hdl.handle.net/11336/212479
identifier_str_mv Agorrody, Guillermo; Peclat, Thais R.; Peluso, Gonzalo; Gonano, Luis Alberto; Santos, Leonardo; et al.; Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 166; 5-2022; 11-22
0022-2828
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://linkinghub.elsevier.com/retrieve/pii/S0022282822000190
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yjmcc.2022.01.008
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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
dc.publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
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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score 13.070432

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