Evidence map›Paper›PMID 27417588›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Mice Expressing Low Levels of CalDAG-GEFI Exhibit Markedly Impaired Platelet Activation With Minor Impact on Hemostasis.

Raymond Piatt, David S Paul, Robert H Lee, Steven E McKenzie, Leslie V Parise, Dale O Cowley, Brian C Cooley, Wolfgang Bergmeier

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022
    Review
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  6. Review
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  9. Platelet Signaling Pathways and New Inhibitors.Arteriosclerosis, thrombosis, and vascular biology · 2018
    Review
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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

8 authors at 2 institutions in 1 country.

Raymond PiattFrom the McAllister Heart Institute, University of North Carolina, Chapel Hill (R.P., D.S.P., R.H.L., W.B.); Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (S.E.M.); Department of Biochemistry and Biophysics (L.V.P., W.B.), Animal Models Core (D.O.C.), and Rodent Advanced Surgical Core (B.C.C.), University of North Carolina at Chapel Hill.
David S PaulFrom the McAllister Heart Institute, University of North Carolina, Chapel Hill (R.P., D.S.P., R.H.L., W.B.); Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (S.E.M.); Department of Biochemistry and Biophysics (L.V.P., W.B.), Animal Models Core (D.O.C.), and Rodent Advanced Surgical Core (B.C.C.), University of North Carolina at Chapel Hill.
Robert H LeeFrom the McAllister Heart Institute, University of North Carolina, Chapel Hill (R.P., D.S.P., R.H.L., W.B.); Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (S.E.M.); Department of Biochemistry and Biophysics (L.V.P., W.B.), Animal Models Core (D.O.C.), and Rodent Advanced Surgical Core (B.C.C.), University of North Carolina at Chapel Hill.
Steven E McKenzieFrom the McAllister Heart Institute, University of North Carolina, Chapel Hill (R.P., D.S.P., R.H.L., W.B.); Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (S.E.M.); Department of Biochemistry and Biophysics (L.V.P., W.B.), Animal Models Core (D.O.C.), and Rodent Advanced Surgical Core (B.C.C.), University of North Carolina at Chapel Hill.
Leslie V PariseFrom the McAllister Heart Institute, University of North Carolina, Chapel Hill (R.P., D.S.P., R.H.L., W.B.); Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (S.E.M.); Department of Biochemistry and Biophysics (L.V.P., W.B.), Animal Models Core (D.O.C.), and Rodent Advanced Surgical Core (B.C.C.), University of North Carolina at Chapel Hill.
Dale O CowleyFrom the McAllister Heart Institute, University of North Carolina, Chapel Hill (R.P., D.S.P., R.H.L., W.B.); Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (S.E.M.); Department of Biochemistry and Biophysics (L.V.P., W.B.), Animal Models Core (D.O.C.), and Rodent Advanced Surgical Core (B.C.C.), University of North Carolina at Chapel Hill.
Brian C CooleyFrom the McAllister Heart Institute, University of North Carolina, Chapel Hill (R.P., D.S.P., R.H.L., W.B.); Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (S.E.M.); Department of Biochemistry and Biophysics (L.V.P., W.B.), Animal Models Core (D.O.C.), and Rodent Advanced Surgical Core (B.C.C.), University of North Carolina at Chapel Hill.
Wolfgang BergmeierFrom the McAllister Heart Institute, University of North Carolina, Chapel Hill (R.P., D.S.P., R.H.L., W.B.); Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (S.E.M.); Department of Biochemistry and Biophysics (L.V.P., W.B.), Animal Models Core (D.O.C.), and Rodent Advanced Surgical Core (B.C.C.), University of North Carolina at Chapel Hill. bergmeie@email.unc.edu.
University of North Carolina at Chapel Hill · USThomas Jefferson University · US

Funding

Thrombosis Models CoreP01HL120846 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ABRAMS, CHARLES S. · 2014 to 2018
$12.2M
Protein CoreP01HL110860 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI RAUOVA, LUBICA · 2012 to 2016
$11.4M
Research Training in Hematology at UNC Chapel HillT32HL007149 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Nigel S. Key · 1985 to 2026
$8.6M
Platelet AADACL1 in thrombosis, lipidomics and signalingR01HL126124 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HOLLY, STEPHEN P, PARISE, LESLIE V. · 2015 to 2018
$1.5M
Novel strategies to prevent FcgRIIA-dependent platelet activation and thrombosisR01HL106009 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BERGMEIER, WOLFGANG · 2011 to 2014
$1.5M
Spatial regulation of platelet activation by Podoplanin-Clec2 signalingR01HL121650 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BERGMEIER, WOLFGANG, KAHN, MARK L · 2014 to 2017
$1.2M
NHLBI NIH HHS P01 HL110860NHLBI NIH HHS P01 HL120846NHLBI NIH HHS R01 HL106009NHLBI NIH HHS R01 HL121650NHLBI NIH HHS R01 HL126124NHLBI NIH HHS T32 HL007149
6 · The paper itself

Abstract

objectiveThe tight regulation of platelet adhesiveness, mediated by the αIIbβ3 integrin, is critical for hemostasis and prevention of thrombosis. We recently demonstrated that integrin affinity in platelets is controlled by the guanine nucleotide exchange factor, CalDAG-GEFI (CD-GEFI), and its target, RAP1. In this study, we investigated whether low-level expression of CD-GEFI leads to protection from thrombosis without pathological bleeding in mice. APPROACH AND

resultsCdg1(low) mice were generated by knockin of human CD-GEFI cDNA into the mouse Cdg1 locus. CD-GEFI expression in platelets from Cdg1(low) mice was reduced by ≈90% when compared with controls. Activation of RAP1 and αIIbβ3 was abolished at low agonist concentrations and partially inhibited at high agonist concentrations in Cdg1(low) platelets. Consistently, the aggregation response of Cdg1(low) platelets was weaker than that of wild-type platelets, but more efficient than that observed in Cdg1(-/-) platelets. Importantly, Cdg1(low) mice were strongly protected from arterial and immune complex-mediated thrombosis, with only minimal impact on primary hemostasis.

conclusionsTogether, our studies suggest the partial inhibition of CD-GEFI function as a powerful new approach to safely prevent thrombotic complications.

Indexed as

HemostasisPlatelet ActivationAnimalsBlood PlateletsDisease Models, AnimalGenotypeGuanine Nucleotide Exchange FactorsHumansMice, TransgenicMutationPhenotypePlatelet AggregationPlatelet Glycoprotein GPIIb-IIIa Complexrap1 GTP-Binding ProteinsSignal TransductionThrombosisGuanine Nucleotide Exchange FactorsPlatelet Glycoprotein GPIIb-IIIa Complexrap1 GTP-Binding ProteinsRASGRP2 protein, humanhemostasismouseplateletsignal transductionsmall GTPasethrombosis

Identifiers

PMID27417588
PMCPMC5001889
OpenAlexW2469273342

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.