Evidence map›Paper›PMID 26224885›Full record

ArticleDiabetes2016

ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity.

Vaibhav B Patel, Jun Mori, Brent A McLean, Ratnadeep Basu, Subhash K Das, Tharmarajan Ramprasath, Nirmal Parajuli, Josef M Penninger, Maria B Grant, Gary D Lopaschuk and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 1 pooled it
8.5field-weighted citation impact, top 2% 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

160 citing papers in PubMed, 1 synthesis or guideline pooled it, 260 citations in OpenAlex.

  1. Association of epicardial adipose tissue with the severity and adverse clinical outcomes of COVID-19: A meta-analysis.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2022
    Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Role of epicardial adipose tissue in heart failure with preserved ejection fraction: An emerging molecular mechanism and therapeutic potential.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
    Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Vaibhav B PatelDivision of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Jun MoriMazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
Brent A McLeanMazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Ratnadeep BasuDivision of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Subhash K DasDivision of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Tharmarajan RamprasathDivision of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Nirmal ParajuliDivision of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Josef M PenningerInstitute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
Maria B GrantDepartment of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.
Gary D LopaschukMazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
Gavin Y OuditDivision of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada Department of Physiology, University of Alberta, Edmonton, Alberta, Canada Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada gavin.oudit@ualberta.ca.
University of Alberta · CAIndiana University – Purdue University Indianapolis · USInstitute of Molecular Biotechnology · AT

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance.

Indexed as

Diet, High-FatAdiponectinAdipose TissueAMP-Activated Protein KinasesAngiotensin-Converting Enzyme 2Angiotensin IAnimalsBlood GlucoseBlotting, WesternEnzyme-Linked Immunosorbent AssayGlucose IntoleranceHeartHeart FailureHumansInflammationInsulin ResistanceACE2 protein, humanAce2 protein, mouseAdiponectinAMP-Activated Protein KinasesAngiotensin-Converting Enzyme 2Angiotensin Iangiotensin I (1-7)Blood GlucosePeptide FragmentsPeptidyl-Dipeptidase ATumor Necrosis Factor-alphaVasodilator Agents

Identifiers

PMID26224885
PMCPMC4686955
OpenAlexW2153075644

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.