Logo do repositório
 
Publicação

Soluble guanylate cyclase stimulation improves cardiac function and mitochondrial activity in a rat model of early-stage heart failure with preserved ejection fraction

2025-10Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorVázquez-Abuín, Xocas
dc.contributor.authorMoraña-Fernández, Sandra
dc.contributor.authorAragón-Herrera, Alana
dc.contributor.authorSandner, Peter
dc.contributor.authorThomitzek, Karen
dc.contributor.authorGarcía-Seara, Javier
dc.contributor.authorBravo, Susana B.
dc.contributor.authorOtero-Santiago, Manuel
dc.contributor.authorde la Fuente-López, Pablo
dc.contributor.authorTilves-Bellas, Carlos
dc.contributor.authorRodrigues, Alexandre
dc.contributor.authorGonçalves, Alexandre
dc.contributor.authorPereira Morais, Juliana
dc.contributor.authorMorais, Juliana
dc.contributor.authorAlves, Inês N.
dc.contributor.authorSousa-Mendes, Cláudia
dc.contributor.authorFalcão-Pires, Inês
dc.contributor.authorTarazón, Estefanía
dc.contributor.authorRoselló-Lletí, Esther
dc.contributor.authorPortolés, Manuel
dc.contributor.authorGualillo, Oreste
dc.contributor.authorGonzález-Juanatey, José Ramón
dc.contributor.authorFeijóo-Bandín, Sandra
dc.contributor.authorLago, Francisca
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS)
dc.contributor.pblElsevier
dc.date.accessioned2025-09-10T21:37:51Z
dc.date.available2025-09-10T21:37:51Z
dc.date.issued2025-10
dc.descriptionFunding Information: This work was supported by a research grant of Bayer AG (DEU), the National Institute of Health \u201CFondo de Investigaciones Sanitarias del Instituto de Salud Carlos III\u201D Madrid, Spain [PI21/01145, PI24/00114 and CIBER de Enfermedades Cardiovasculares (CIBERCV)]; Axencia Galega de Innovaci\u00F3n (GAIN): Axudas do programa de consolidaci\u00F3n e estruturaci\u00F3n de unidades de investigaci\u00F3n competitivas (GPC IN607B 2021 108 and GPC IN607B 2024\u201302). S.M.-F. was funded by a predoctoral research grant from GAIN-Xunta de Galicia (Spain), X.V.-A. was funded by Sociedad Espa\u00F1ola de Cardiolog\u00EDa (RLD_SEC2016 and SECAINC-INV-ICC 23/02) and A.A.-H. postdoctoral contract is funded by the Sara Borrell Program of the Instituto de Salud Carlos III (ISCIII) and previously was funded by a postdoctoral research grant from Health Research Institute of Santiago de Compostela (IDIS) and Foundation of IDIS (FIDIS). Publisher Copyright: © 2025 The Authors
dc.description.abstractTargeting cardiac mitochondrial dysfunction and cardiac metabolic reprogramming is critical for improving chronic heart failure (HF) treatment. While the soluble guanylate cyclase stimulator vericiguat has shown promise in treating HF with reduced ejection fraction (HFrEF), its effects on HF with preserved ejection fraction (HFpEF), particularly on myocardial bioenergetics, remain undefined. This study aimed to clarify the effects of vericiguat on cardiac function and metabolism in a preclinical model of early-stage HF. Obese ZSF1 (Zucker fatty and spontaneously hypertensive) rats were randomized to receive standard care (n = 10) or vericiguat (3 mg/kg/d p.o.) (n = 10) treatment for 4 weeks. ZSF1 lean rats (n = 10) served as controls. Vericiguat improved diastolic function, reduced cardiac hypertrophy and fibrosis and enhanced cardiac mitochondrial basal respiration, upregulating the levels of several mitochondrial electron transport chain proteins from complexes I, II, III and V, along with the ADP/ATP translocase 1 mRNA levels, and partially reversing mitochondrial cristae diffuse dissolution observed in obese control rat hearts. Vericiguat treatment increased cardiac levels of phosphoproteins involved in the pentose phosphate pathway (PPP) (6-phosphogluconolactonase and 6-phosphogluconate dehydrogenase) and in the Krebs cycle (malate dehydrogenase and aspartate aminotransferase), while normalizing the mRNA levels of the master regulator of calcium uptake by the mitochondria (MICU1). Furthermore, vericiguat restored the cardiac levels of key metabolites of the PPP such as 6-phosphogluconate, D-ribose 5-phosphate, and arginine, that were diminished in the obese control group. In conclusion, vericiguat elicits beneficial functional and metabolic responses at cardiac level in an animal model of early-stage HFpEF.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent12909351
dc.identifier.doi10.1016/j.biopha.2025.118439
dc.identifier.issn0753-3322
dc.identifier.otherPURE: 128517706
dc.identifier.otherPURE UUID: d6e5ce3d-4291-4c3a-bb07-bb7e760c3d22
dc.identifier.otherScopus: 105013113001
dc.identifier.otherPubMed: 40795471
dc.identifier.urihttp://hdl.handle.net/10362/187774
dc.identifier.urlhttps://www.scopus.com/pages/publications/105013113001
dc.language.isoeng
dc.peerreviewedyes
dc.subjectDiastolic dysfunction
dc.subjectHeart failure with preserved ejection fraction
dc.subjectMitochondria
dc.subjectProteome
dc.subjectSoluble guanylate cyclase stimulator
dc.subjectZSF1
dc.subjectPharmacology
dc.titleSoluble guanylate cyclase stimulation improves cardiac function and mitochondrial activity in a rat model of early-stage heart failure with preserved ejection fractionen
dc.typejournal article
degois.publication.titleBiomedicine and Pharmacotherapy
degois.publication.volume191
dspace.entity.typePublication
person.familyNameMorais
person.givenNameJuliana
person.identifier.ciencia-idB210-1529-F980
person.identifier.orcid0000-0003-3783-6074
person.identifier.scopus-author-id57209240036
rcaap.rightsopenAccess
relation.isAuthorOfPublicationaced2b31-d6e7-4589-a1d0-f4efdde7cf4e
relation.isAuthorOfPublication.latestForDiscoveryaced2b31-d6e7-4589-a1d0-f4efdde7cf4e

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
1-s2.0-S075333222500633X-main.pdf
Tamanho:
12.31 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

NMS: CINTESIS - Artigos em revista internacional com arbitragem científica