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    Poster Networking

    Platelets and Megakaryocytes

    Poster Networking Session

    PB0377 - Analysis of hepatic TPO production after myocardial infarction and partial hepatectomy

    Sunday, June 25, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      Presenting Author(s)

    • NS

      Niloofar Salehzadeh, MS (she/her/hers)

      Doctoral Researcher
      Institute of experimental vascular medicine
      Düsseldorf, Nordrhein-Westfalen, Germany

      • Co-Author(s)

    • FR

      Friedrich WB Reusswig

      Postdoctoral Research Fellow
      Department of Vascular- and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany
      Duesseldorf, Nordrhein-Westfalen, Germany

    • Sevgi C. Cengiz, PhD (she/her/hers)

      Postdoctoral Researcher
      Institute of Experimantal Vascular Medicine
      Düsseldorf, Nordrhein-Westfalen, Germany

    • KV

      Kristina Vogel

      Postdoctoral researcher
      Institute of Biochemistry and Molecular Biology II
      Düsseldorf, Nordrhein-Westfalen, Germany

    • JS

      Jürgen Scheller

      Group Leader
      Institute of Biochemistry and Molecular Biology II
      Düsseldorf, Nordrhein-Westfalen, Germany

    • ME

      Margitta Elvers

      Professor
      Clinic for Vascular- and Endovascular Surgery, University Clinic of the Heinrich-Heine- University Düsseldorf, Düsseldorf, Germany.
      Duesseldorf, Nordrhein-Westfalen, Germany

    Background: Side effects of partial hepatectomy (PHx) as well as acute myocardial infarction (AMI) are characterized thrombocytopenia. Recent studies provided evidence for a prominent role of the interleukin-6 receptor (IL-6R) in modulation of thrombopoietin (TPO) biosynthesis in hepatic tissue. However, until now no study analyzed IL-6R dependent liver signaling in regards to hepatic TPO synthesis

    Aims: The aim of the study is to analyze the effect of IL-6R signaling on TPO hemostasis in naïve mice and shortly after PHx or AMI.

    Methods: In vitro and in vivo experiments using mice after PHx or AMI. Compared to wildtype mice we also analyzed IL-6R deficient animals.

    Results: In general, within the first 24h after PHx or AMI a reduced platelet count is observed. This thrombocytopenia is recovered until 7 days after surgery in both models. In both models an increased hepatic TPO gene expression as well as enhanced TPO plasma accumulation was observed. This increase in TPO production is mediated through an increase in the IL-6R mediated signaling cascade, including an enhanced phosphorylation of STAT3 at early time points. We could show that TPO synthesis is controlled via IL-6R signaling as we analyzed IL-6R deficient mice after PHx, which showed severe thrombocytopenia after PHx compared to controls. Additionally enhanced expression of hepatic Ashwell-Morell Receptor (AMR) subunits were measured in hepatic tissue of both inflammatory surgery models. Interestingly, genetic deletion of either receptor (IL-6R or AMR) resulted in a compensatory increase in the other receptor subunit. The beneficial effects on platelet count restoration after PHx and AMI are accompanied by subsequently enhanced splenic megakaryopoiesis after PHx and AMI.

    Conclusion(s): These results indicate that both after PHx and AMI platelet turnover is massively regulated, driven by IL-6R. However, this is the first study to compare regulatory systems to control the platelet count via enhanced expression of TPO.