Effect of empagliflozin on cardiac biomarkers in a zebrafish model of heart failure: clues to the EMPA-REG OUTCOME trial?
Mol Cell Biochem
; 433(1-2): 97-102, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28391552
ABSTRACT
The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin was recently reported to reduce heart failure-associated hospitalizations and cardiovascular mortality amongst individuals with type 2 diabetes at high cardiovascular risk. We sought to elucidate the underlying mechanism(s) for these protective effects using a validated zebrafish heart failure model to evaluate the impact of empagliflozin on the expression of biomarkers of heart failure and mortality. We used aristolochic acid (AA) to induce heart failure in developing cmlc2GFP transgenic zebrafish embryos and monitored BNP signaling in nppbLuc transgenic zebrafish with a luciferase reporter assay. Empagliflozin markedly reduced the morphological and functional cardiac changes induced by AA; dampened AA-enhanced expression of brain natriuretic peptide and atrial natriuretic peptide; and reduced embryonic mortality. Furthermore, morpholino-mediated knockdown of the slc5A2 gene mimicked the changes evoked by empagliflozin in developing zebrafish embryos previously exposed to AA. We report herein the first mechanistic data demonstrating a salutary benefit of SGLT2 inhibition on critical pathways of heart failure signaling. These findings provide important translational clues to the cardiovascular benefits documented in the EMPA-REG OUTCOME study.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos Benzidrílicos
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Peixe-Zebra
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Glucosídeos
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Insuficiência Cardíaca
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá