Evidence map›Paper›PMID 28391552›Full record

ArticleMolecular and cellular biochemistry2017

Effect of empagliflozin on cardiac biomarkers in a zebrafish model of heart failure: clues to the EMPA-REG OUTCOME trial?

Xingjuan Shi, Subodh Verma, Junghwa Yun, Koroboshka Brand-Arzamendi, Krishna K Singh, Xiangdong Liu, Ankit Garg, Adrian Quan, Xiao-Yan Wen

Abstract read
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In one paragraph

Article in Molecular and cellular biochemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
9.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.

  1. Pooled it
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  3. Trial
  4. Review
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  6. SGLT2 inhibitors: how do they affect the cardiac cells.Molecular and cellular biochemistry · 2025
    Review
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  8. Article
  9. Article
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  12. Use of Animal Models for Investigating Cardioprotective Roles of SGLT2 Inhibitors.Journal of cardiovascular translational research · 2023
    Review
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  15. Article
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  18. Benefits of SGLT2 inhibitors in arrhythmias.Frontiers in cardiovascular medicine · 2022
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Xingjuan ShiZebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Department of Medicine and Physiology, University of Toronto, 209 Victoria Street, LKSKI Rm 519, Toronto, ON, M5B 1T8, Canada.
Subodh VermaDivision of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. vermasu@smh.ca.
Junghwa YunZebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Department of Medicine and Physiology, University of Toronto, 209 Victoria Street, LKSKI Rm 519, Toronto, ON, M5B 1T8, Canada.
Koroboshka Brand-ArzamendiZebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Department of Medicine and Physiology, University of Toronto, 209 Victoria Street, LKSKI Rm 519, Toronto, ON, M5B 1T8, Canada.
Krishna K SinghDivision of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
Xiangdong LiuKey Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, China.
Ankit GargDivision of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
Adrian QuanDivision of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
Xiao-Yan WenZebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Department of Medicine and Physiology, University of Toronto, 209 Victoria Street, LKSKI Rm 519, Toronto, ON, M5B 1T8, Canada. wenx@smh.ca.
St. Michael's Hospital · CAUniversity of Toronto · CASoutheast University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 cmlc2::GFP transgenic zebrafish embryos and monitored BNP signaling in nppb::Luc 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.

Indexed as

Heart FailureAnimalsAnimals, Genetically ModifiedAristolochic AcidsBenzhydryl CompoundsBiomarkersClinical Trials as TopicDisease Models, AnimalFemaleGlucosidesHumansMaleZebrafisharistolochic acid CAristolochic AcidsBenzhydryl CompoundsBiomarkersempagliflozinGlucosidesBiomarkersEmpagliflozinHeart failureZebrafish

Identifiers

PMID28391552
OpenAlexW2604729247

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.