The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , |
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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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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_version_ |
1808128699580547072 |