Evidence map›Paper›PMID 26232087›Full record

ArticleCirculation. Cardiovascular genetics2015

Superoxide Dismutase 1 In Vivo Ameliorates Maternal Diabetes Mellitus-Induced Apoptosis and Heart Defects Through Restoration of Impaired Wnt Signaling.

Fang Wang, Steven A Fisher, Jianxiang Zhong, Yanqing Wu, Peixin Yang

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

Article in Circulation. Cardiovascular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Genetic and Environmental Contributors To Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2025
    Review
  8. Article
  9. Congenital heart defects and consanguinity: An analysis of the Sidra cardiac registry data in Qatar.International journal of cardiology. Congenital heart disease · 2024
    Article
  10. Article
  11. Review
  12. Molecular Pathways and Animal Models of d-Transposition of the Great Arteries.Advances in experimental medicine and biology · 2024
    Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review
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

5 authors at 1 institution in 1 country.

Fang WangFrom the Departments of Obstetrics, Gynecology, and Reproductive Sciences (F.W., J.Z., Y.W., P.Y.), Medicine (S.A.F.), and Biochemistry and Molecular Biology (P.Y.), School of Medicine, University of Maryland, Baltimore.
Steven A FisherFrom the Departments of Obstetrics, Gynecology, and Reproductive Sciences (F.W., J.Z., Y.W., P.Y.), Medicine (S.A.F.), and Biochemistry and Molecular Biology (P.Y.), School of Medicine, University of Maryland, Baltimore.
Jianxiang ZhongFrom the Departments of Obstetrics, Gynecology, and Reproductive Sciences (F.W., J.Z., Y.W., P.Y.), Medicine (S.A.F.), and Biochemistry and Molecular Biology (P.Y.), School of Medicine, University of Maryland, Baltimore.
Yanqing WuFrom the Departments of Obstetrics, Gynecology, and Reproductive Sciences (F.W., J.Z., Y.W., P.Y.), Medicine (S.A.F.), and Biochemistry and Molecular Biology (P.Y.), School of Medicine, University of Maryland, Baltimore.
Peixin YangFrom the Departments of Obstetrics, Gynecology, and Reproductive Sciences (F.W., J.Z., Y.W., P.Y.), Medicine (S.A.F.), and Biochemistry and Molecular Biology (P.Y.), School of Medicine, University of Maryland, Baltimore. pyang@fpi.umaryland.edu.
University of Maryland, Baltimore · US

Funding

Tissue Hypoxia in Cardiac MorphogenesisR01HL065314 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI FISHER, STEVEN A. · 2000 to 2013
$4.4M
Apoptotic Mechanism of Maternal Diabetes-Induced Neural Tube DefectsR01DK083243 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI YANG, PEIXIN · 2010 to 2019
$3.1M
Molecular Signalling Pathways and Cellular Stress in Diabetic EmbryopathyR01DK103024 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI REECE, E. ALBERT, YANG, PEIXIN · 2014 to 2017
$1.7M
Autophagy and its Regulation in Diabetic EmbryopathyR01DK101972 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI YANG, PEIXIN · 2014 to 2017
$1.6M
NHLBI NIH HHS R01 HL065314NHLBI NIH HHS R01HL65314NIDDK NIH HHS R01 DK083243NIDDK NIH HHS R01DK083243NIDDK NIH HHS R01 DK101972NIDDK NIH HHS R01DK101972NIDDK NIH HHS R01 DK103024NIDDK NIH HHS R01DK103024
6 · The paper itself

Abstract

backgroundOxidative stress is manifested in embryos exposed to maternal diabetes mellitus, yet specific mechanisms for diabetes mellitus-induced heart defects are not defined. Gene deletion of intermediates of Wingless-related integration (Wnt) signaling causes heart defects similar to those observed in embryos from diabetic pregnancies. We tested the hypothesis that diabetes mellitus-induced oxidative stress impairs Wnt signaling, thereby causing heart defects, and that these defects can be rescued by transgenic overexpression of the reactive oxygen species scavenger superoxide dismutase 1 (SOD1). METHODS AND

resultsWild-type (WT) and SOD1-overexpressing embryos from nondiabetic WT control dams and nondiabetic/diabetic WT female mice mated with SOD1 transgenic male mice were analyzed. No heart defects were observed in WT and SOD1 embryos under nondiabetic conditions. WT embryos of diabetic dams had a 26% incidence of cardiac outlet defects that were suppressed by SOD1 overexpression. Insulin treatment reduced blood glucose levels and heart defects. Diabetes mellitus increased superoxide production, canonical Wnt antagonist expression, caspase activation, and apoptosis and suppressed cell proliferation. Diabetes mellitus suppressed Wnt signaling intermediates and Wnt target gene expression in the embryonic heart, each of which were reversed by SOD1 overexpression. Hydrogen peroxide and peroxynitrite mimicked the inhibitory effect of high glucose on Wnt signaling, which was abolished by the SOD1 mimetic, tempol.

conclusionsThe oxidative stress of diabetes mellitus impairs Wnt signaling and causes cardiac outlet defects that are rescued by SOD1 overexpression. This suggests that targeting of components of the Wnt5a signaling pathway may be a viable strategy for suppression of congenital heart defects in fetuses of diabetic pregnancies.

Indexed as

Oxidative StressPregnancy in DiabeticsAnimalsApoptosisDiabetes ComplicationsDiabetes Mellitus, ExperimentalFemaleGene ExpressionHeartHeart Defects, CongenitalHumansHydrogen PeroxideMaleMiceMice, TransgenicPeroxynitrous AcidHydrogen PeroxidePeroxynitrous AcidSOD1 protein, humanSod1 protein, mouseSuperoxide DismutaseSuperoxide Dismutase-1Wnt-5a ProteinWnt5a protein, mouseWnt Proteinsapoptosiscongenitaldiabetes mellitusheart defectsoxidative stresspregnancyWnt signaling pathway

Identifiers

PMID26232087
PMCPMC4618088
OpenAlexW1842741418

What OpenQuestion holds

Textmetadata
LicenceTDM
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.