Evidence map›Paper›PMID 23894596›Full record

ArticlePloS one2013

Impairment of endothelial-myocardial interaction increases the susceptibility of cardiomyocytes to ischemia/reperfusion injury.

Thorsten M Leucker, Zhi-Dong Ge, Jesse Procknow, Yanan Liu, Yang Shi, Martin Bienengraeber, David C Warltier, Judy R Kersten

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

27 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Endothelial cell dysfunction in cardiac disease: driver or consequence?Frontiers in cell and developmental biology · 2023
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. AnExperimental and therapeutic medicine · 2017
    Article
  18. Article
  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

8 authors at 1 institution in 1 country.

Thorsten M LeuckerDepartment of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Zhi-Dong Ge
Jesse Procknow
Yanan Liu
Yang Shi
Martin Bienengraeber
David C Warltier
Judy R Kersten
Medical College of Wisconsin · US

Funding

Stem Cell CoreP01GM066730 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI DASH, RANJAN K · 2003 to 2019
$23.6M
MECHANISMS OF MYOCARDIAL ISCHEMIC INJURY IN DIABETESR01HL063705 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI KERSTEN, JUDY R. · 2001 to 2010
$3.0M
Anesthesiology Research Training ProgramT32GM089586 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI EBERT, THOMAS JAY · 2010 to 2019
$1.5M
NHLBI NIH HHS HL 063705NHLBI NIH HHS R01 HL063705NIGMS NIH HHS GM 066730NIGMS NIH HHS P01 GM066730NIGMS NIH HHS T32 GM089586
6 · The paper itself

Abstract

Endothelial-myocardial interactions may be critically important for ischemia/reperfusion injury. Tetrahydrobiopterin (BH4) is a required cofactor for nitric oxide (NO) production by endothelial NO synthase (eNOS). Hyperglycemia (HG) leads to significant increases in oxidative stress, oxidizing BH4 to enzymatically incompetent dihydrobiopterin. How alterations in endothelial BH4 content impact myocardial ischemia/reperfusion injury remains elusive. The aim of this study was to examine the effect of endothelial-myocardial interaction on ischemia/reperfusion injury, with an emphasis on the role of endothelial BH4 content. Langendorff-perfused mouse hearts were treated by triton X-100 to produce endothelial dysfunction and subsequently subjected to 30 min of ischemia followed by 2 h of reperfusion. The recovery of left ventricular systolic and diastolic function during reperfusion was impaired in triton X-100 treated hearts compared with vehicle-treated hearts. Cardiomyocytes (CMs) were co-cultured with endothelial cells (ECs) and subsequently subjected to 2 h of hypoxia followed by 2 h of reoxygenation. Addition of ECs to CMs at a ratio of 1∶3 significantly increased NO production and decreased lactate dehydrogenase activity compared with CMs alone. This EC-derived protection was abolished by HG. The addition of 100 µM sepiapterin (a BH4 precursor) or overexpression of GTP cyclohydrolase 1 (the rate-limiting enzyme for BH4 biosynthesis) in ECs by gene trasfer enhanced endothelial BH4 levels, the ratio of eNOS dimer/monomer, eNOS phosphorylation, and NO production and decreased lactate dehydrogenase activity in the presence of HG. These results demonstrate that increased BH4 content in ECs by either pharmacological or genetic approaches reduces myocardial damage during hypoxia/reoxygenation in the presence of HG. Maintaining sufficient endothelial BH4 is crucial for cardioprotection against hypoxia/reoxygenation injury.

Indexed as

Cell CommunicationAnimalsBiopterinsDisease SusceptibilityEndothelial CellsGlucoseHyperglycemiaMaleMiceMyocytes, CardiacNitric OxideNitric Oxide Synthase Type IIIPhosphorylationProtein MultimerizationProtein Structure, QuaternaryPterinsBiopterinsGlucoseNitric OxideNitric Oxide Synthase Type IIIPterinssapropterinsepiapterin

Identifiers

PMID23894596
PMCPMC3718730
OpenAlexW2045485623

What OpenQuestion holds

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LicenceCC BY
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.