Evidence map›Paper›PMID 29579152›Full record

ArticleCardiovascular research2018

Cardioprotection induced by a brief exposure to acetaldehyde: role of aldehyde dehydrogenase 2.

Cintia Bagne Ueta, Juliane Cruz Campos, Rudá Prestes E Albuquerque, Vanessa Morais Lima, Marie-Hélène Disatnik, Angélica Bianchini Sanchez, Che-Hong Chen, Marisa Helena Gennari de Medeiros, Wenjin Yang, Daria Mochly-Rosen and 1 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Cardiovascular research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 6% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. ALDH2 Enzyme Deficiency in Diabetic Cardiomyopathy.International journal of molecular sciences · 2025
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. [Research progress of acetaldehyde dehydrogenase 2 in liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022
    Article
  14. Article
  15. Review
  16. Article
  17. Identification of Small Airway Epithelium-Related Hub Genes in Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2022
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Cintia Bagne UetaDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Juliane Cruz CamposDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Rudá Prestes E AlbuquerqueDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Vanessa Morais LimaDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Marie-Hélène DisatnikDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, USA.
Angélica Bianchini SanchezDepartment of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil.
Che-Hong ChenDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, USA.
Marisa Helena Gennari de MedeirosDepartment of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil.
Wenjin YangForesee Pharmaceuticals Co., Ltd., Taipei, Taiwan.
Daria Mochly-RosenDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, USA.
Julio Cesar Batista FerreiraDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Universidade de São Paulo · BRStanford University · US

Funding

Mechanisms of Ethanol-Induced Cardiac ProtectionR37AA011147 · NIAAA · STANFORD UNIVERSITY · PI MOCHLY-ROSEN, DARIA · 2009 to 2018
$5.3M
NIAAA NIH HHS R37 AA011147
6 · The paper itself

Abstract

Aims: We previously demonstrated that acute ethanol administration protects the heart from ischaemia/reperfusion (I/R) injury thorough activation of aldehyde dehydrogenase 2 (ALDH2). Here, we characterized the role of acetaldehyde, an intermediate product from ethanol metabolism, and its metabolizing enzyme, ALDH2, in an ex vivo model of cardiac I/R injury. Methods and results: We used a combination of homozygous knock-in mice (ALDH2*2), carrying the human inactivating point mutation ALDH2 (E487K), and a direct activator of ALDH2, Alda-1, to investigate the cardiac effect of acetaldehyde. The ALDH2*2 mice have impaired acetaldehyde clearance, recapitulating the human phenotype. Yet, we found a similar infarct size in wild type (WT) and ALDH2*2 mice. Similar to ethanol-induced preconditioning, pre-treatment with 50 μM acetaldehyde increased ALDH2 activity and reduced cardiac injury in hearts of WT mice without affecting cardiac acetaldehyde levels. However, acetaldehyde pre-treatment of hearts of ALDH2*2 mice resulted in a three-fold increase in cardiac acetaldehyde levels and exacerbated I/R injury. Therefore, exogenous acetaldehyde appears to have a bimodal effect in I/R, depending on the ALDH2 genotype. Further supporting an ALDH2 role in cardiac preconditioning, pharmacological ALDH2 inhibition abolished ethanol-induced cardioprotection in hearts of WT mice, whereas a selective activator, Alda-1, protected ALDH2*2 against ethanol-induced cardiotoxicity. Finally, either genetic or pharmacological inhibition of ALDH2 mitigated ischaemic preconditioning. Conclusion: Taken together, our findings suggest that low levels of acetaldehyde are cardioprotective whereas high levels are damaging in an ex vivo model of I/R injury and that ALDH2 is a major, but not the only, regulator of cardiac acetaldehyde levels and protection from I/R.

Indexed as

AcetaldehydeAldehyde Dehydrogenase, MitochondrialAnimalsCardiotoxicityCell LineDisease Models, AnimalDose-Response Relationship, DrugEnzyme ActivationGene Knock-In TechniquesGenotypeHumansMaleMice, Inbred C57BLMice, TransgenicMyocardial InfarctionMyocardial Reperfusion InjuryAcetaldehydeAldehyde Dehydrogenase, MitochondrialALDH2 protein, human

Identifiers

PMID29579152
PMCPMC5967552
OpenAlexW2789584521

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.