Evidence mapPaperPMID 37624927Full record

ArticleBlood2023

The oxylipin analog CS585 prevents platelet activation and thrombosis through activation of the prostacyclin receptor.

Livia Stanger, Adriana Yamaguchi, Pooja Yalavarthi, Sylviane Lambert, Devin Gilmore, Andrew Rickenberg, Catherine Luke, Kiran Kumar, Andrea T Obi, Andrew White and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2023. 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
4.0field-weighted citation impact, top 5% 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, 18 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Deficiency in platelet 12-lipoxygenase exacerbates inflammation and disease severity during SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Antiplatelet strategies: past, present, and future.Journal of thrombosis and haemostasis : JTH · 2023
    Review
  15. Explore the Staging of Cerebral Venous Thrombosis Through Fibrinolytic Indicators.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Livia StangerDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, MI.ORCID 0000-0001-6034-0646
Adriana YamaguchiDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, MI.
Pooja YalavarthiDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, MI.
Sylviane LambertDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, MI.
Devin GilmoreDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, MI.
Andrew RickenbergDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, MI.ORCID 0009-0003-4367-1461
Catherine LukeDepartment of Vascular Surgery, University of Michigan Medical School, Ann Arbor, MI.
Kiran KumarDepartment of Vascular Surgery, University of Michigan Medical School, Ann Arbor, MI.
Andrea T ObiDepartment of Vascular Surgery, University of Michigan Medical School, Ann Arbor, MI.ORCID 0000-0001-7613-2366
Andrew WhiteDepartment of Medicinal Chemistry, University of Michigan Medical School, Ann Arbor, MI.
Niklas BerghInstitute of Medicine, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0002-7440-2366
Björn DahlöfInstitute of Medicine, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0001-6050-388X
Michael HolinstatDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, MI.ORCID 0000-0001-5100-1933
University of Michigan · USSahlgrenska University Hospital · SEUniversity of Gothenburg · SE

Funding

TRAINING IN MOLECULAR AND CELLULAR CARDIOLOGYT32HL007853 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1996 to 2025
$2.8M
Interdepartmental Training in Pharmacological SciencesT32GM140223 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$640k
Myeloid TLR4 epigenetic regulation and signaling in accelerating venous thrombus resolutionK08HL155408 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 to 2025
$298k
NCATS NIH HHS TL1 TR002242NCATS NIH HHS UL1 TR002240NHLBI NIH HHS K08 HL155408NHLBI NIH HHS T32 HL007853NIGMS NIH HHS R35 GM131835NIGMS NIH HHS T32 GM140223
6 · The paper itself

Abstract

Cardiovascular disease remains the primary cause of morbidity and mortality globally. Platelet activation is critical for maintaining hemostasis and preventing the leakage of blood cells from the vessel. There has been a paucity in the development of new drugs to target platelet reactivity. Recently, the oxylipin 12(S)-hydroxy-eicosatrienoic acid (12-HETrE), which is produced in platelets, was shown to limit platelet reactivity by activating the prostacyclin receptor. Here, we demonstrated the synthesis of a novel analog of 12-HETrE, known as CS585. Human blood and mouse models of hemostasis and thrombosis were assessed for the ability of CS585 to attenuate platelet activation and thrombosis without increasing the risk of bleeding. Human platelet activation was assessed using aggregometry, flow cytometry, western blot analysis, total thrombus formation analysis system, microfluidic perfusion chamber, and thromboelastography. Hemostasis, thrombosis, and bleeding assays were performed in mice. CS585 was shown to potently target the prostacyclin receptor on the human platelet, resulting in a highly selective and effective mechanism for the prevention of platelet activation. Furthermore, CS585 was shown to inhibit platelet function in human whole blood ex vivo, prevent thrombosis in both small and large vessels in mouse models, and exhibit long-lasting prevention of clot formation. Finally, CS585 was not observed to perturb coagulation or increase the risk of bleeding in the mouse model. Hence, CS585 represents a new validated target for the treatment of thrombotic diseases without the risk of bleeding or off-target activation observed with other prostaglandin receptor agonists.

Indexed as

OxylipinsThrombosisAnimalsBlood PlateletsHemorrhageHemostasisHumansMicePlatelet ActivationPlatelet AggregationReceptors, EpoprostenolOxylipinsReceptors, Epoprostenol

Identifiers

PMID37624927
PMCPMC10656727
OpenAlexW4386156787

What Socratic holds

Textmetadata
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 Socratic graph.