IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35331-0.html
   My bibliography  Save this article

Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction

Author

Listed:
  • Erik Klapproth

    (Technische Universität Dresden)

  • Anke Witt

    (Technische Universität Dresden)

  • Pauline Klose

    (Technische Universität Dresden)

  • Johanna Wiedemann

    (Technische Universität Dresden)

  • Nikitha Vavilthota

    (Technische Universität Dresden)

  • Stephan R. Künzel

    (Technische Universität Dresden)

  • Susanne Kämmerer

    (Technische Universität Dresden)

  • Mario Günscht

    (Technische Universität Dresden)

  • David Sprott

    (Technische Universität Dresden)

  • Mathias Lesche

    (Technische Universität Dresden)

  • Fabian Rost

    (Technische Universität Dresden)

  • Andreas Dahl

    (Technische Universität Dresden)

  • Erik Rauch

    (Endotherm GmbH)

  • Lars Kattner

    (Endotherm GmbH)

  • Silvio Weber

    (Technische Universität Dresden)

  • Peter Mirtschink

    (Technische Universität Dresden)

  • Irakli Kopaliani

    (Technische Universität Dresden)

  • Kaomei Guan

    (Technische Universität Dresden)

  • Kristina Lorenz

    (Julius-Maximilians-University of Würzburg
    Leibniz-Institut für Analytische Wissenschaften -ISAS- e.V.)

  • Paul Saftig

    (Biochemical Institute, Christian-Albrechts-Universität Kiel)

  • Michael Wagner

    (Technische Universität Dresden
    Technische Universität Dresden)

  • Ali El-Armouche

    (Technische Universität Dresden)

Abstract

After myocardial infarction the innate immune response is pivotal in clearing of tissue debris as well as scar formation, but exaggerated cytokine and chemokine secretion with subsequent leukocyte infiltration also leads to further tissue damage. Here, we address the value of targeting a previously unknown a disintegrin and metalloprotease 10 (ADAM10)/CX3CL1 axis in the regulation of neutrophil recruitment early after MI. We show that myocardial ADAM10 is distinctly upregulated in myocardial biopsies from patients with ischemia-driven cardiomyopathy. Intriguingly, upon MI in mice, pharmacological ADAM10 inhibition as well as genetic cardiomycyte-specific ADAM10 deletion improves survival with markedly enhanced heart function and reduced scar size. Mechanistically, abolished ADAM10-mediated CX3CL1 ectodomain shedding leads to diminished IL-1β-dependent inflammation, reduced neutrophil bone marrow egress as well as myocardial tissue infiltration. Thus, our data shows a conceptual insight into how acute MI induces chemotactic signaling via ectodomain shedding in cardiomyocytes.

Suggested Citation

  • Erik Klapproth & Anke Witt & Pauline Klose & Johanna Wiedemann & Nikitha Vavilthota & Stephan R. Künzel & Susanne Kämmerer & Mario Günscht & David Sprott & Mathias Lesche & Fabian Rost & Andreas Dahl , 2022. "Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35331-0
    DOI: 10.1038/s41467-022-35331-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35331-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35331-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35331-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.