Evidence map›Paper›PMID 27616880›Full record

ArticleDrug design, development and therapy2016

Ticagrelor promotes atherosclerotic plaque stability in a mouse model of advanced atherosclerosis.

Michael R Preusch, Jonas Rusnak, Kathrin Staudacher, Carolin Mogler, Lorenz Uhlmann, Philipp Sievers, Florian Bea, Hugo A Katus, Erwin Blessing, Ingo Staudacher

Open access · goldAbstract read
In one paragraph

Article in Drug design, development and therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Article
  3. PScientific reports · 2021
    Article
  4. Review
  5. Article
  6. Beneficial Effects of Ticagrelor on Oxidized Low-Density Lipoprotein (ox-LDL)-Induced Apoptosis in Human Umbilical Vein Endothelial Cells.Medical science monitor : international medical journal of experimental and clinical research · 2019
    Article
  7. Article
  8. Article
  9. Article
  10. The role of P2YCellular and molecular life sciences : CMLS · 2019
    Review
  11. Platelets Are at the Nexus of Vascular Diseases.Frontiers in cardiovascular medicine · 2019
    Review
  12. Article
  13. Article
  14. The P2YFrontiers in pharmacology · 2018
    Article
  15. 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

10 authors at 1 institution in 1 country.

Michael R PreuschDepartment of Internal Medicine III.
Jonas RusnakDepartment of Internal Medicine III.
Kathrin StaudacherDepartment of Neonatology.
Carolin MoglerDepartment of Pathology.
Lorenz UhlmannInstitute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
Philipp SieversDepartment of Internal Medicine III.
Florian BeaDepartment of Internal Medicine III.
Hugo A KatusDepartment of Internal Medicine III.
Erwin BlessingDepartment of Internal Medicine III.
Ingo StaudacherDepartment of Internal Medicine III.
Heidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThere is increasing evidence supporting the role of platelets in atherosclerotic vascular disease. The G-protein-coupled receptor P2Y12 is a central mediator of platelet activation and aggregation but has also been linked to platelet-independent vascular disease. Ticagrelor is an oral P2Y12 antagonist that is used as a standard treatment in patients after acute myocardial infarction. However, the effects of ticagrelor on advanced atherosclerosis have not been investigated. MATERIALS AND

methodsTwenty-week-old apolipoprotein-E-deficient mice received standard chow or standard chow supplemented with 0.15% ticagrelor (approximately 270 mg/kg/day) for 25 weeks. The lesion area was evaluated in the aortic sinus by Movat's pentachrome staining and lesion composition, thickness of the fibrous cap, and size of the necrotic core evaluated by morphometry. RAW 264.7 macrophages were serum starved and treated with ticagrelor in vitro for the detection and quantification of apoptosis. In addition, oxLDL uptake in RAW 264.7 macrophages was evaluated.

resultsA trend toward the reduction of total lesion size was detected. However, data did not reach the levels of significance (control, n=11, 565,881 μm(2) [interquartile range {IQR} 454,778-603,925 μm(2)] versus ticagrelor, n=13, 462,595 μm(2) [IQR 379,740-546,037 μm(2)]; P=0.1). A significant reduction in the relative area of the necrotic core (control, n=11, 0.46 [IQR 0.4-0.51] versus ticagrelor, n=13, 0.34 [IQR 0.31-0.39]; P=0.008), and a significant increase in fibrous caps thickness (control, n=11, 3.7 μm [IQR 3.4-4.2 μm] versus ticagrelor, n=13, 4.7 [IQR 4.3-5.5 μm], P=0.04) were seen in ticagrelor-treated mice. In vitro studies demonstrated a reduction in apoptotic RAW 264.7 macrophages (control 0.07±0.03 versus ticagrelor 0.03±0.03; P=0.0002) when incubated with ticagrelor. Uptake of oxLDL in RAW 264.7 was significantly reduced when treated with ticagrelor (control 9.2 [IQR 5.3-12.9] versus ticagrelor 6.4 [IQR 2.5-9.5], P=0.02).

conclusionThe present study demonstrates for the first time a plaque-stabilizing effect of ticagrelor in a model of advanced vascular disease, potentially induced by a reduction of oxLDL uptake or an inhibition of apoptosis as seen in vitro.

Indexed as

Disease Models, AnimalAdenosineAdministration, OralAnimalsApolipoproteins EApoptosisAtherosclerosisDose-Response Relationship, DrugMacrophagesMiceMice, Inbred C57BLMice, KnockoutPlaque, AtheroscleroticStructure-Activity RelationshipTicagrelorAdenosineApolipoproteins ETicagrelorapoE mouseapoptosisatherosclerosisinflammationoxLDLP2Y12plateletsticagrelor

Identifiers

PMID27616880
PMCPMC5008449
OpenAlexW2508468592

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.