The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis

Detalhes bibliográficos
Autor(a) principal: da Silva, Vitor Loureiro [UNESP]
Data de Publicação: 2022
Outros Autores: de Souza, Sérgio Luiz Borges, Mota, Gustavo Augusto Ferreira, Campos, Dijon H. S., Melo, Alexandre Barroso, Vileigas, Danielle Fernandes, Sant’ana, Paula Grippa, Coelho, Priscila Murucci, Bazan, Silméia Garcia Zanati, Leopoldo, André Soares, Cicogna, Antônio Carlos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.36660/abc.20200618
http://hdl.handle.net/11449/223604
Resumo: Background: Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling. Objective: To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis. Methods: Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05. Results: Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger. Conclusion: Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.
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spelling The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic StenosisAortic stenosisCalcium handling proteinsHeart failureIsolated cardiomyocytesPapillary muscleBackground: Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling. Objective: To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis. Methods: Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05. Results: Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger. Conclusion: Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade de São Paulo Departamento de Medicina Interna, SPUniversidade Estadual Paulista-Clínica Médica, SPUniversidade Federal do Espírito Santo Departamento de Desportos, ESUniversidade Estadual Paulista-Clínica Médica, SPFAPESP: 2015/20013-5Universidade de São Paulo (USP)Universidade Estadual Paulista (UNESP)Universidade Federal do Espírito Santo (UFES)da Silva, Vitor Loureiro [UNESP]de Souza, Sérgio Luiz BorgesMota, Gustavo Augusto FerreiraCampos, Dijon H. S.Melo, Alexandre BarrosoVileigas, Danielle FernandesSant’ana, Paula GrippaCoelho, Priscila MurucciBazan, Silméia Garcia ZanatiLeopoldo, André SoaresCicogna, Antônio Carlos2022-04-28T19:51:45Z2022-04-28T19:51:45Z2022-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article464-475http://dx.doi.org/10.36660/abc.20200618Arquivos Brasileiros de Cardiologia, v. 118, n. 2, p. 464-475, 2022.1678-41700066-782Xhttp://hdl.handle.net/11449/22360410.36660/abc.202006182-s2.0-85126076429Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengArquivos Brasileiros de Cardiologiainfo:eu-repo/semantics/openAccess2022-04-28T19:51:46Zoai:repositorio.unesp.br:11449/223604Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:46:47.872986Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis
title The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis
spellingShingle The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis
da Silva, Vitor Loureiro [UNESP]
Aortic stenosis
Calcium handling proteins
Heart failure
Isolated cardiomyocytes
Papillary muscle
title_short The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis
title_full The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis
title_fullStr The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis
title_full_unstemmed The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis
title_sort The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis
author da Silva, Vitor Loureiro [UNESP]
author_facet da Silva, Vitor Loureiro [UNESP]
de Souza, Sérgio Luiz Borges
Mota, Gustavo Augusto Ferreira
Campos, Dijon H. S.
Melo, Alexandre Barroso
Vileigas, Danielle Fernandes
Sant’ana, Paula Grippa
Coelho, Priscila Murucci
Bazan, Silméia Garcia Zanati
Leopoldo, André Soares
Cicogna, Antônio Carlos
author_role author
author2 de Souza, Sérgio Luiz Borges
Mota, Gustavo Augusto Ferreira
Campos, Dijon H. S.
Melo, Alexandre Barroso
Vileigas, Danielle Fernandes
Sant’ana, Paula Grippa
Coelho, Priscila Murucci
Bazan, Silméia Garcia Zanati
Leopoldo, André Soares
Cicogna, Antônio Carlos
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Estadual Paulista (UNESP)
Universidade Federal do Espírito Santo (UFES)
dc.contributor.author.fl_str_mv da Silva, Vitor Loureiro [UNESP]
de Souza, Sérgio Luiz Borges
Mota, Gustavo Augusto Ferreira
Campos, Dijon H. S.
Melo, Alexandre Barroso
Vileigas, Danielle Fernandes
Sant’ana, Paula Grippa
Coelho, Priscila Murucci
Bazan, Silméia Garcia Zanati
Leopoldo, André Soares
Cicogna, Antônio Carlos
dc.subject.por.fl_str_mv Aortic stenosis
Calcium handling proteins
Heart failure
Isolated cardiomyocytes
Papillary muscle
topic Aortic stenosis
Calcium handling proteins
Heart failure
Isolated cardiomyocytes
Papillary muscle
description Background: Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling. Objective: To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis. Methods: Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05. Results: Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger. Conclusion: Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-28T19:51:45Z
2022-04-28T19:51:45Z
2022-01-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.36660/abc.20200618
Arquivos Brasileiros de Cardiologia, v. 118, n. 2, p. 464-475, 2022.
1678-4170
0066-782X
http://hdl.handle.net/11449/223604
10.36660/abc.20200618
2-s2.0-85126076429
url http://dx.doi.org/10.36660/abc.20200618
http://hdl.handle.net/11449/223604
identifier_str_mv Arquivos Brasileiros de Cardiologia, v. 118, n. 2, p. 464-475, 2022.
1678-4170
0066-782X
10.36660/abc.20200618
2-s2.0-85126076429
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Arquivos Brasileiros de Cardiologia
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 464-475
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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