Evidence map›Paper›PMID 38900242›Full record

ArticleCardiovascular drugs and therapy2025

Blocking the TRAIL-DR5 Pathway Reduces Cardiac Ischemia-Reperfusion Injury by Decreasing Neutrophil Infiltration and Neutrophil Extracellular Traps Formation.

Xuance Wang, Ran Xie, Dan Zhao, Guiling Wang, Lijie Zhang, Wei Shi, Yanyan Chen, Tingting Mo, Yuxin Du, Xuefei Tian and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular drugs and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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  5. Article
  6. Review
  7. Advances in the study of death receptor 5.Frontiers in pharmacology · 2025
    Review
  8. 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

15 authors.

Xuance Wang *Joint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.ORCID 0000-0001-6571-3413
Ran Xie *Joint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Dan ZhaoJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Guiling WangJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Lijie ZhangJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Wei ShiJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Yanyan ChenJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Tingting MoJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Yuxin DuJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Xuefei TianJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Wanjun WangJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Run CaoJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.
Yuanfang MaJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China.ORCID 0000-0001-5635-2660
Yinxiang WeiJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China. yxwei@henu.edu.cn.ORCID 0000-0002-1699-1115
Yaohui WangJoint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, 475004, P.R. China. wangyaohui2017@henu.edu.cn.ORCID 0000-0003-0165-6573

Funding

Henan Medical Science and Technique Foundation No.SBGJ202102195Key Programme No.U22A20382National Natural Science Foundation of China No.82101913Natural Science Foundation of Henan Province No.242300421021Science and Technology Innovation Talents in Universities of Henan Province No.22HASTIT046
6 · The paper itself

Abstract

purposeAcute myocardial infarction (AMI) is a leading cause of mortality. Neutrophils penetrate injured heart tissue during AMI or ischemia-reperfusion (I/R) injury and produce inflammatory factors, chemokines, and extracellular traps that exacerbate heart injury. Inhibition of the TRAIL-DR5 pathway has been demonstrated to alleviate cardiac ischemia-reperfusion injury in a leukocyte-dependent manner. However, it remains unknown whether TRAIL-DR5 signaling is involved in regulating neutrophil extracellular traps (NETs) release.

methodsThis study used various models to examine the effects of activating the TRAIL-DR5 pathway with soluble mouse TRAIL protein and inhibiting the TRAIL-DR5 signaling pathway using DR5 knockout mice or mDR5-Fc fusion protein on NETs formation and cardiac injury. The models used included a co-culture model involving bone marrow-derived neutrophils and primary cardiomyocytes and a model of myocardial I/R in mice.

resultsNETs formation is suppressed by TRAIL-DR5 signaling pathway inhibition, which can lessen cardiac I/R injury. This intervention reduces the release of adhesion molecules and chemokines, resulting in decreased neutrophil infiltration and inhibiting NETs production by downregulating PAD4 in neutrophils.

conclusionThis work clarifies how the TRAIL-DR5 signaling pathway regulates the neutrophil response during myocardial I/R damage, thereby providing a scientific basis for therapeutic intervention targeting the TRAIL-DR5 signaling pathway in myocardial infarction.

Indexed as

Extracellular TrapsMyocardial InfarctionMyocardial Reperfusion InjuryMyocytes, CardiacNeutrophil InfiltrationNeutrophilsReceptors, TNF-Related Apoptosis-Inducing LigandTNF-Related Apoptosis-Inducing LigandAnimalsCoculture TechniquesDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, KnockoutSignal TransductionReceptors, TNF-Related Apoptosis-Inducing LigandTNF-Related Apoptosis-Inducing LigandTnfsf10 protein, mouseCardiac ischemia–reperfusionDR5NETsPAD4TRAIL

Identifiers

PMID38900242
PMCPMC12602621

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Registered trials

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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.