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

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dc.contributor.authorda Silva, Vitor Loureiro [UNESP]
dc.contributor.authorde Souza, Sérgio Luiz Borges
dc.contributor.authorMota, Gustavo Augusto Ferreira
dc.contributor.authorCampos, Dijon H. S.
dc.contributor.authorMelo, Alexandre Barroso
dc.contributor.authorVileigas, Danielle Fernandes
dc.contributor.authorSant’ana, Paula Grippa
dc.contributor.authorCoelho, Priscila Murucci
dc.contributor.authorBazan, Silméia Garcia Zanati
dc.contributor.authorLeopoldo, André Soares
dc.contributor.authorCicogna, Antônio Carlos
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade Federal do Espírito Santo (UFES)
dc.date.accessioned2022-04-28T19:51:45Z
dc.date.available2022-04-28T19:51:45Z
dc.date.issued2022-01-01
dc.description.abstractBackground: 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.en
dc.description.affiliationUniversidade de São Paulo Departamento de Medicina Interna, SP
dc.description.affiliationUniversidade Estadual Paulista-Clínica Médica, SP
dc.description.affiliationUniversidade Federal do Espírito Santo Departamento de Desportos, ES
dc.description.affiliationUnespUniversidade Estadual Paulista-Clínica Médica, SP
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2015/20013-5
dc.format.extent464-475
dc.identifierhttp://dx.doi.org/10.36660/abc.20200618
dc.identifier.citationArquivos Brasileiros de Cardiologia, v. 118, n. 2, p. 464-475, 2022.
dc.identifier.doi10.36660/abc.20200618
dc.identifier.issn1678-4170
dc.identifier.issn0066-782X
dc.identifier.scopus2-s2.0-85126076429
dc.identifier.urihttp://hdl.handle.net/11449/223604
dc.language.isoeng
dc.relation.ispartofArquivos Brasileiros de Cardiologia
dc.sourceScopus
dc.subjectAortic stenosis
dc.subjectCalcium handling proteins
dc.subjectHeart failure
dc.subjectIsolated cardiomyocytes
dc.subjectPapillary muscle
dc.titleThe Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosisen
dc.typeArtigo

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