Evidence map›Paper›PMID 25287063›Full record

ArticleCirculation research2014

Thymidine phosphorylase participates in platelet signaling and promotes thrombosis.

Wei Li, Alba Gigante, Maria-Jesus Perez-Perez, Hong Yue, Michio Hirano, Thomas M McIntyre, Roy L Silverstein

Open access · bronzeAbstract readVideo-Audio Media
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

40 citing papers in PubMed, 60 citations in OpenAlex.

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  20. The matricellular protein CCN3 supports lung endothelial homeostasis and function.American journal of physiology. Lung cellular and molecular physiology · 2023
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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 5 institutions in 1 country.

Wei LiFrom the Department of Cellular and Molecular Medicine, Lerner Research Institute, The Cleveland Clinic, OH (W.L., T.M.M.); Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (W.L., T.M.M.); Instituto de Quimica Medica, Consejo Superior De Investigaciones Cientificas (IQM-CSIC), Madrid, Spain (A.G.,M.-J.P.-P.); Department of Biological Sciences, Case Western Reserve University, Cleveland, OH (H.Y.); Department of Neurology, Columbia University Medical Center, New York, NY (M.H.); and Department of Medicine, Medical College of Wisconsin and Blood Research Institute, Blood Center of Wisconsin, Milwaukee (R.L.S.) liw4@ccf.org.
Alba GiganteFrom the Department of Cellular and Molecular Medicine, Lerner Research Institute, The Cleveland Clinic, OH (W.L., T.M.M.); Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (W.L., T.M.M.); Instituto de Quimica Medica, Consejo Superior De Investigaciones Cientificas (IQM-CSIC), Madrid, Spain (A.G.,M.-J.P.-P.); Department of Biological Sciences, Case Western Reserve University, Cleveland, OH (H.Y.); Department of Neurology, Columbia University Medical Center, New York, NY (M.H.); and Department of Medicine, Medical College of Wisconsin and Blood Research Institute, Blood Center of Wisconsin, Milwaukee (R.L.S.).
Maria-Jesus Perez-PerezFrom the Department of Cellular and Molecular Medicine, Lerner Research Institute, The Cleveland Clinic, OH (W.L., T.M.M.); Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (W.L., T.M.M.); Instituto de Quimica Medica, Consejo Superior De Investigaciones Cientificas (IQM-CSIC), Madrid, Spain (A.G.,M.-J.P.-P.); Department of Biological Sciences, Case Western Reserve University, Cleveland, OH (H.Y.); Department of Neurology, Columbia University Medical Center, New York, NY (M.H.); and Department of Medicine, Medical College of Wisconsin and Blood Research Institute, Blood Center of Wisconsin, Milwaukee (R.L.S.).
Hong YueFrom the Department of Cellular and Molecular Medicine, Lerner Research Institute, The Cleveland Clinic, OH (W.L., T.M.M.); Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (W.L., T.M.M.); Instituto de Quimica Medica, Consejo Superior De Investigaciones Cientificas (IQM-CSIC), Madrid, Spain (A.G.,M.-J.P.-P.); Department of Biological Sciences, Case Western Reserve University, Cleveland, OH (H.Y.); Department of Neurology, Columbia University Medical Center, New York, NY (M.H.); and Department of Medicine, Medical College of Wisconsin and Blood Research Institute, Blood Center of Wisconsin, Milwaukee (R.L.S.).
Michio HiranoFrom the Department of Cellular and Molecular Medicine, Lerner Research Institute, The Cleveland Clinic, OH (W.L., T.M.M.); Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (W.L., T.M.M.); Instituto de Quimica Medica, Consejo Superior De Investigaciones Cientificas (IQM-CSIC), Madrid, Spain (A.G.,M.-J.P.-P.); Department of Biological Sciences, Case Western Reserve University, Cleveland, OH (H.Y.); Department of Neurology, Columbia University Medical Center, New York, NY (M.H.); and Department of Medicine, Medical College of Wisconsin and Blood Research Institute, Blood Center of Wisconsin, Milwaukee (R.L.S.).
Thomas M McIntyreFrom the Department of Cellular and Molecular Medicine, Lerner Research Institute, The Cleveland Clinic, OH (W.L., T.M.M.); Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (W.L., T.M.M.); Instituto de Quimica Medica, Consejo Superior De Investigaciones Cientificas (IQM-CSIC), Madrid, Spain (A.G.,M.-J.P.-P.); Department of Biological Sciences, Case Western Reserve University, Cleveland, OH (H.Y.); Department of Neurology, Columbia University Medical Center, New York, NY (M.H.); and Department of Medicine, Medical College of Wisconsin and Blood Research Institute, Blood Center of Wisconsin, Milwaukee (R.L.S.).
Roy L SilversteinFrom the Department of Cellular and Molecular Medicine, Lerner Research Institute, The Cleveland Clinic, OH (W.L., T.M.M.); Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (W.L., T.M.M.); Instituto de Quimica Medica, Consejo Superior De Investigaciones Cientificas (IQM-CSIC), Madrid, Spain (A.G.,M.-J.P.-P.); Department of Biological Sciences, Case Western Reserve University, Cleveland, OH (H.Y.); Department of Neurology, Columbia University Medical Center, New York, NY (M.H.); and Department of Medicine, Medical College of Wisconsin and Blood Research Institute, Blood Center of Wisconsin, Milwaukee (R.L.S.).
Cleveland Clinic Lerner College of Medicine · USVersiti Blood Center of Wisconsin · USCase Western Reserve University · USCleveland Clinic · USColumbia University Irving Medical Center · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
ROLE OF MICROPARTICLES IN THE ANTI-PHOSPHOLIPID SYNDROMEP50HL081011 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS · 2006 to 2010
$12.9M
REGULATION OF TENSIONP01NS011766 · NINDS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SCHON, ERIC A. · 1985 to 2007
$9.1M
Tech-CoreP01HD080642 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI QUINZII, CATARINA M. · 2014 to 2018
$7.8M
Circulating Age-related Lipid Mediators in ThrombosisR01HL092747 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS M · 2007 to 2010
$2.2M
Systemic Oxidized Phospholipids in Mitochondrial Dysfunction of Alcoholic InjuryR01AA017748 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS M · 2008 to 2012
$1.9M
Mechanistic Role of CD36 in ThrombosisR01HL111614 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI SILVERSTEIN, ROY L · 2013 to 2017
$1.7M
MOLECULAR PATHOGENESIS OF MNGIE SYNDROMER01HD037529 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HIRANO, MICHIO · 1999 to 2001
$581k
NCATS NIH HHS UL1 TR000439NHLBI NIH HHS HL092747NHLBI NIH HHS HL81011NHLBI NIH HHS P50 HL081011NHLBI NIH HHS R01 HL092747NHLBI NIH HHS R01 HL111614NIAAA NIH HHS AA017748NIAAA NIH HHS R01 AA017748NICHD NIH HHS P01 HD080642NINDS NIH HHS P01 NS011766
6 · The paper itself

Abstract

rationalePlatelets contain abundant thymidine phosphorylase (TYMP), which is highly expressed in diseases with high risk of thrombosis, such as atherosclerosis and type II diabetes mellitus.

objectiveTo test the hypothesis that TYMP participates in platelet signaling and promotes thrombosis. METHODS AND

resultsBy using a ferric chloride (FeCl3)-induced carotid artery injury thrombosis model, we found time to blood flow cessation was significantly prolonged in Tymp(-/-) and Tymp(+/-) mice compared with wild-type mice. Bone marrow transplantation and platelet transfusion studies demonstrated that platelet TYMP was responsible for the antithrombotic phenomenon in the TYMP-deficient mice. Collagen-, collagen-related peptide-, adenosine diphosphate-, or thrombin-induced platelet aggregation were significantly attenuated in Tymp(+/-) and Tymp(-/-) platelets, and in wild type or human platelets pretreated with TYMP inhibitor KIN59. Tymp deficiency also significantly decreased agonist-induced P-selectin expression. TYMP contains an N-terminal SH3 domain-binding proline-rich motif and forms a complex with the tyrosine kinases Lyn, Fyn, and Yes in platelets. TYMP-associated Lyn was inactive in resting platelets, and TYMP trapped and diminished active Lyn after collagen stimulation. Tymp/Lyn double haploinsufficiency diminished the antithrombotic phenotype of Tymp(+/-) mice. TYMP deletion or inhibition of TYMP with KIN59 dramatically increased platelet-endothelial cell adhesion molecule 1 tyrosine phosphorylation and diminished collagen-related peptide- or collagen-induced AKT phosphorylation. In vivo administration of KIN59 significantly inhibited FeCl3-induced carotid artery thrombosis without affecting hemostasis.

conclusionsTYMP participates in multiple platelet signaling pathways and regulates platelet activation and thrombosis. Targeting TYMP might be a novel antiplatelet and antithrombosis therapy.

Indexed as

Signal TransductionAmino Acid SequenceAnimalsBlood PlateletsBone Marrow TransplantationChloridesEnzyme InhibitorsFerric CompoundsHaploinsufficiencyHumansMaleMice, Inbred C57BLMice, KnockoutMolecular Sequence DataPhenotypePhosphorylationChloridesEnzyme Inhibitorsferric chlorideFerric CompoundsFyn protein, mouselyn protein-tyrosine kinasePlatelet Aggregation InhibitorsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-fynProto-Oncogene Proteins c-yesSelenoprotein Psrc-Family KinasesThymidine PhosphorylaseTYMP protein, humanTymp protein, mouseYes1 protein, mouseintracellular signalingplateletthrombosisthymidine phosphorylase

Identifiers

PMID25287063
PMCPMC4258140
OpenAlexW2140646825

What OpenQuestion holds

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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.