Evidence map›Paper›PMID 27633389›Full record

ArticleJournal of the American Heart Association2016

MKEY, a Peptide Inhibitor of CXCL4-CCL5 Heterodimer Formation, Protects Against Stroke in Mice.

Yifang Fan, Xiaoxing Xiong, Yongming Zhang, Dongmei Yan, Zhihong Jian, Baohui Xu, Heng Zhao

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

Article in Journal of the American Heart Association, 2016. 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
2.7field-weighted citation impact, top 10% 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, 48 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023
    Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Molecular Biology of Atherosclerotic Ischemic Strokes.International journal of molecular sciences · 2020
    Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. The dual role of platelet-innate immune cell interactions in thrombo-inflammation.Research and practice in thrombosis and haemostasis · 2020
    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

7 authors at 3 institutions in 2 countries.

Yifang FanDepartment of Neurosurgery, Stanford University, Stanford, CA Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Xiaoxing XiongDepartment of Neurosurgery, Stanford University, Stanford, CA Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Yongming ZhangDepartment of Neurosurgery, Stanford University, Stanford, CA.
Dongmei YanDepartment of Neurosurgery, Stanford University, Stanford, CA.
Zhihong JianDepartment of Neurosurgery, Stanford University, Stanford, CA Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Baohui XuDepartment of Surgery, Stanford University, Stanford, CA.
Heng ZhaoDepartment of Neurosurgery, Stanford University, Stanford, CA hzhao@stanford.edu.
Stanford University · USCapital Medical University · CNWuhan University · CN

Funding

Protective mechanisms of ischemic postconditioningR01NS064136 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 2010 to 2020
$3.1M
NINDS NIH HHS R01 NS064136
6 · The paper itself

Abstract

backgroundMKEY, a synthetic cyclic peptide inhibitor of CXCL4-CCL5 heterodimer formation, has been shown to protect against atherosclerosis and aortic aneurysm formation by mediating inflammation, but whether it modulates neuroinflammation and brain injury has not been studied. We therefore studied the role of MKEY in stroke-induced brain injury in mice. METHODS AND

resultsMKEY was injected into mice after stroke with 60 minutes of middle cerebral artery occlusion. Infarct volume and neurological deficit scores were measured. Protein levels of CCL5 and its receptor CCR5 were detected by Western blot and fluorescence-activated cell sorting (FACS), respectively. Numbers of microglia-derived macrophages (MiMΦs) and monocyte-derived MΦs (MoMΦs) in the brain, and their subsets, based on the surface markers CD45, CD11b, CCR2, CX3CR1, and Ly6C, were analyzed by FACS. MΦs and neutrophil infiltration in the ischemic brain were stained with CD68 and myeloperoxidase (MPO), respectively, and assessed by immunofluorescent confocal microscopy. The results showed that expressions of CCL5 and its receptor CCR5, were increased in the ischemic brain after stroke. MKEY injection significantly reduced infarct sizes and improved neurological deficit scores measured 72 hours after stroke. In addition, MKEY injection inhibited the number of MoMΦs, but not MiMΦs, in the ischemic brain. Furthermore, MKEY inhibited protein expression levels of Ly6C,CCR2, and CX3CR1 on MoMΦs. Lastly, the confocal study also suggests that the number of CD68-positive MΦs and MPO-positive neutrophils was inhibited by MKEY injection.

conclusionsMKEY injection protects against stroke-induced brain injury, probably by inhibiting MoMΦ-mediated neuroinflammation.

Indexed as

AnimalsBlotting, WesternBrainChemokine CCL5DimerizationFlow CytometryInfarction, Middle Cerebral ArteryMacrophagesMaleMiceMicroscopy, ConfocalMicroscopy, FluorescenceNeutrophilsPeptides, CyclicPlatelet Factor 4StrokeCcl5 protein, mouseChemokine CCL5MKEY peptidePeptides, CyclicPlatelet Factor 4cerebrovascular disease/strokeimmunologyinfarct or infarctioninflammation

Identifiers

PMID27633389
PMCPMC5079025
OpenAlexW2520095852

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.