Evidence map›Paper›PMID 29802205›Full record

ArticleCirculation2018

Functional Relevance of the Anaphylatoxin Receptor C3aR for Platelet Function and Arterial Thrombus Formation Marks an Intersection Point Between Innate Immunity and Thrombosis.

Reinhard J Sauter, Manuela Sauter, Edimara S Reis, Frederic N Emschermann, Henry Nording, Sonja Ebenhöch, Peter Kraft, Patrick Münzer, Maximilian Mauler, Johannes Rheinlaender and 11 more

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

Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

80 citing papers in PubMed, 116 citations in OpenAlex.

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  10. Beyond hemostasis, the immunomodulatory nature of platelets.Research and practice in thrombosis and haemostasis · 2025
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  19. Activation of platelets and the complement system in mice withAmerican journal of physiology. Lung cellular and molecular physiology · 2024
    Article
  20. Review

20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 2 countries.

Reinhard J SauterDepartment of Cardiology and Cardiovascular Medicine, University Clinic (R.J.S., H.N., P.M., T.G., O.B., M.G., H.F.L.), Eberhard Karls-University Tübingen, Germany.
Manuela SauterSection for Cardioimmunology (R.J.S., M.S., F.N.E., H.N., S.E., H.F.L.), Eberhard Karls-University Tübingen, Germany.
Edimara S ReisDepartment of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia (E.S.R., J.D.L.).
Frederic N EmschermannSection for Cardioimmunology (R.J.S., M.S., F.N.E., H.N., S.E., H.F.L.), Eberhard Karls-University Tübingen, Germany.
Henry NordingDepartment of Cardiology and Cardiovascular Medicine, University Clinic (R.J.S., H.N., P.M., T.G., O.B., M.G., H.F.L.), Eberhard Karls-University Tübingen, Germany.
Sonja EbenhöchSection for Cardioimmunology (R.J.S., M.S., F.N.E., H.N., S.E., H.F.L.), Eberhard Karls-University Tübingen, Germany.
Peter KraftDepartment of Neurology, University of Würzburg, Germany (P.K.).
Patrick MünzerDepartment of Cardiology and Cardiovascular Medicine, University Clinic (R.J.S., H.N., P.M., T.G., O.B., M.G., H.F.L.), Eberhard Karls-University Tübingen, Germany.
Maximilian MaulerCardiology and Angiology I, Heart Center Freiburg University and Faculty of Medicine (M.M., D.D.), University of Freiburg, Germany.
Johannes RheinlaenderInstitute of Applied Physics (J.R., T.E.S.), Eberhard Karls-University Tübingen, Germany.
Johannes MadlungProteom Center, Interfaculty Institute for Cell Biology (J.M.), Eberhard Karls-University Tübingen, Germany.
Frank EdlichInstitute of Biochemistry (F.E.), University of Freiburg, Germany.
Tilman E SchäfferInstitute of Applied Physics (J.R., T.E.S.), Eberhard Karls-University Tübingen, Germany.
Sven G MeuthDepartment of Neurology, University of Münster, Germany (S.G.M.).
Daniel DuerschmiedCardiology and Angiology I, Heart Center Freiburg University and Faculty of Medicine (M.M., D.D.), University of Freiburg, Germany.
Tobias GeislerDepartment of Cardiology and Cardiovascular Medicine, University Clinic (R.J.S., H.N., P.M., T.G., O.B., M.G., H.F.L.), Eberhard Karls-University Tübingen, Germany.
Oliver BorstDepartment of Cardiology and Cardiovascular Medicine, University Clinic (R.J.S., H.N., P.M., T.G., O.B., M.G., H.F.L.), Eberhard Karls-University Tübingen, Germany.
Meinrad GawazDepartment of Cardiology and Cardiovascular Medicine, University Clinic (R.J.S., H.N., P.M., T.G., O.B., M.G., H.F.L.), Eberhard Karls-University Tübingen, Germany.
Christoph KleinschnitzDepartment of Neurology, University of Essen, Germany (C.K.).
John D LambrisDepartment of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia (E.S.R., J.D.L.).
Harald F LangerDepartment of Cardiology and Cardiovascular Medicine, University Clinic (R.J.S., H.N., P.M., T.G., O.B., M.G., H.F.L.), Eberhard Karls-University Tübingen, Germany.
University of Tübingen · DEUniversity of Freiburg · DEUniversity of Pennsylvania · USKatholisches Klinikum Essen · DEUniversity Hospital Münster · DEUniversity of Würzburg · DE

Funding

Role of complement in kidney disorders: from hemodialysis to transportationP01AI068730 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2007 to 2018
$16.0M
NIAID NIH HHS P01 AI068730
6 · The paper itself

Abstract

backgroundPlatelets have distinct roles in the vascular system in that they are the major mediator of thrombosis, critical for restoration of tissue integrity, and players in vascular inflammatory conditions. In close spatiotemporal proximity, the complement system acts as the first line of defense against invading microorganisms and is a key mediator of inflammation. Whereas the fluid phase cross-talk between the complement and coagulation systems is well appreciated, the understanding of the pathophysiological implications of such interactions is still scant.

methodsWe analyzed coexpression of the anaphylatoxin receptor C3aR with activated glycoprotein IIb/IIIa on platelets of 501 patients with coronary artery disease using flow cytometry; detected C3aR expression in human or murine specimen by polymerase chain reaction, immunofluorescence, Western blotting, or flow cytometry; and examined the importance of platelet C3aR by various in vitro platelet function tests, in vivo bleeding time, and intravital microscopy. The pathophysiological relevance of C3aR was scrutinized with the use of disease models of myocardial infarction and stroke. To approach underlying molecular mechanisms, we identified the platelet small GTPase Rap1b using nanoscale liquid chromatography coupled to tandem mass spectrometry.

resultsWe found a strong positive correlation of platelet complement C3aR expression with activated glycoprotein IIb/IIIa in patients with coronary artery disease and coexpression of C3aR with glycoprotein IIb/IIIa in thrombi obtained from patients with myocardial infarction. Our results demonstrate that the C3a/C3aR axis on platelets regulates distinct steps of thrombus formation such as platelet adhesion, spreading, and Ca

conclusionsOverall, our findings uncover a novel function of the anaphylatoxin C3a for platelet function and thrombus formation, highlighting a detrimental role of imbalanced complement activation in cardiovascular diseases.

Indexed as

Blood CoagulationImmunity, InnateAnimalsBlood PlateletsCalcium SignalingComplement ActivationComplement C3Disease Models, AnimalHumansMice, Inbred C57BLMice, KnockoutMyocardial InfarctionPlatelet ActivationPlatelet Glycoprotein GPIb-IX ComplexPlatelet Glycoprotein GPIIb-IIIa ComplexReceptors, Complementadhesion receptorComplement C3complement C3a receptorPlatelet Glycoprotein GPIb-IX ComplexPlatelet Glycoprotein GPIIb-IIIa ComplexReceptors, Complementanaphylatoxinsblood plateletscomplement system proteinsinflammationmyocardial infarctionstrokethrombosis

Identifiers

PMID29802205
PMCPMC6202244
OpenAlexW2803960610

What OpenQuestion holds

Textmetadata
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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.