Evidence map›Paper›PMID 37364776›Full record

ArticleJournal of thrombosis and haemostasis : JTH2023

Identification of genomic loci regulating platelet plasminogen activator inhibitor-1 in mice.

Amy E Siebert, Marisa A Brake, Stephanie C Verbeek, Alexander J Johnston, Andrew P Morgan, Audrey C Cleuren, Adrianna M Jurek, Caitlin D Schneider, Derrik M Germain, Fabia U Battistuzzi and 6 more

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

Article in Journal of thrombosis and haemostasis : JTH, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 24% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. 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

16 authors at 6 institutions in 1 country.

Amy E SiebertDepartment of Biological Sciences, Oakland University, Rochester, Michigan, USA.
Marisa A BrakeDepartment of Biological Sciences, Oakland University, Rochester, Michigan, USA.
Stephanie C VerbeekDepartment of Biological Sciences, Oakland University, Rochester, Michigan, USA.
Alexander J JohnstonDepartment of Biological Sciences, Oakland University, Rochester, Michigan, USA.
Andrew P MorganDepartment of Medicine, Duke University School of Medicine, Duke University, Durham, North Carolina, USA.
Audrey C CleurenLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
Adrianna M JurekDepartment of Biological Sciences, Oakland University, Rochester, Michigan, USA.
Caitlin D SchneiderDepartment of Biological Sciences, Oakland University, Rochester, Michigan, USA.
Derrik M GermainDepartment of Biological Sciences, Oakland University, Rochester, Michigan, USA.
Fabia U BattistuzziDepartment of Biological Sciences, Oakland University, Rochester, Michigan, USA; Department of Bioengineering, Oakland University, Rochester, Michigan, USA; Centers for Data Science and Big Data Analytics and Biomedical Research, Oakland University, Rochester, Michigan, USA.
Guojing ZhuLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
Darla R MillerDepartment of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Jill M JohnsenDepartment of Medicine, Institute for Stem Cell & Regenerative Medicine, and Center for Cardiovascular Biology, University of Washington, Seattle, Washington, USA.
Fernando Pardo-Manuel de VillenaDepartment of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Matthew T RondinaMolecular Medicine Program, Departments of Internal Medicine and Pathology, the University of Utah, Salt Lake City, Utah, USA; The George E. Wahlen Department of Medical Affairs Medical Center, Salt Lake City, Utah, USA.
Randal J WestrickDepartment of Biological Sciences, Oakland University, Rochester, Michigan, USA; Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA; Department of Bioengineering, Oakland University, Rochester, Michigan, USA; Centers for Data Science and Big Data Analytics and Biomedical Research, Oakland University, Rochester, Michigan, USA; Eye Research Center and Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, Michigan, USA. Electronic address: rjwestrick@oakland.edu.
Oakland University · USUniversity of Michigan · USUniversity of North Carolina at Chapel Hill · USDuke University · USUniversity of Utah · USUniversity of Washington · US

Funding

Translational Control of Megakaryocyte and Platelet Function in SepsisR01HL142804 · NHLBI · UNIVERSITY OF UTAH · PI RONDINA, MATTHEW THOMAS · 2018 to 2021
$1.9M
Thrombosuppressive mechanisms of novel mutants discovered through an ENU mutagenesis screenR01HL135035 · NHLBI · OAKLAND UNIVERSITY · PI WESTRICK, RANDAL J · 2017 to 2021
$1.9M
Platelet-Leukocyte Interactions in SepsisK24HL155856 · NHLBI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI RONDINA, MATTHEW THOMAS · 2021 to 2025
$606k
Identification of the genetic regulators of Plasminogen Activator Inhibitor-1R15HL133907 · NHLBI · OAKLAND UNIVERSITY · PI WESTRICK, RANDAL J · 2016 to 2016
$433k
Platelet Reprogramming During InflammationI01CX001696 · VA · VA SALT LAKE CITY HEALTHCARE SYSTEM · PI Matthew Thomas Rondina · 2018 to 2026
–
CSRD VA I01 CX001696NHLBI NIH HHS K24 HL155856NHLBI NIH HHS R01 HL135035NHLBI NIH HHS R01 HL142804NHLBI NIH HHS R15 HL133907
6 · The paper itself

Abstract

backgroundPlasminogen activator inhibitor-1 (PAI-1, Serpine1) is an important circulating fibrinolysis inhibitor. PAI-1 exists in 2 pools, packaged within platelet α-granules and freely circulating in plasma. Elevated plasma PAI-1 levels are associated with cardiovascular disease. However, little is known about the regulation of platelet PAI-1 (pPAI-1).

objectivesWe investigated the genetic control of pPAI-1 levels in mice and humans.

methodsWe measured pPAI-1 antigen levels via enzyme-linked immunosorbent assay in platelets isolated from 10 inbred mouse strains, including LEWES/EiJ (LEWES) and C57BL/6J (B6). LEWES and B6 were crossed to produce the F1 generation, B6LEWESF1. B6LEWESF1 mice were intercrossed to produce B6LEWESF2 mice. These mice were subjected to genome-wide genetic marker genotyping followed by quantitative trait locus analysis to identify pPAI-1 regulatory loci.

resultsWe identified differences in pPAI-1 between several laboratory strains, with LEWES having pPAI-1 levels more than 10-fold higher than those in B6. Quantitative trait locus analysis of B6LEWESF2 offspring identified a major pPAI-1 regulatory locus on chromosome 5 from 136.1 to 137.6 Mb (logarithm of the odds score, 16.2). Significant pPAI-1 modifier loci on chromosomes 6 and 13 were also identified.

conclusionIdentification of pPAI-1 genomic regulatory elements provides insights into platelet/megakaryocyte-specific and cell type-specific gene expression. This information can be used to design more precise therapeutic targets for diseases where PAI-1 plays a role.

Indexed as

Blood PlateletsPlasminogen Activator Inhibitor 1AnimalsFibrinolysisGenomicsHumansMiceMice, Inbred C57BLQuantitative Trait LociPlasminogen Activator Inhibitor 1blood plateletsfibrinolysisgene expression regulationmegakaryocytesquantitative trait lociserpin E1

Identifiers

PMID37364776
PMCPMC10826891
OpenAlexW4381952818

What OpenQuestion holds

Textmetadata
LicenceTDM
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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.