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Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice

Author

Listed:
  • Carlos E. Bravo-Iñiguez

    (The Feinstein Institutes for Medical Research at Northwell Health
    Elmezzi Graduate School of Molecular Medicine at Northwell Health)

  • Jason R. Fritz

    (The Feinstein Institutes for Medical Research at Northwell Health)

  • Shilpa Shukla

    (The Feinstein Institutes for Medical Research at Northwell Health
    Cohen Children’s Medical Center)

  • Susmita Sarangi

    (The Feinstein Institutes for Medical Research at Northwell Health
    Cohen Children’s Medical Center)

  • Dane A. Thompson

    (The Feinstein Institutes for Medical Research at Northwell Health
    Elmezzi Graduate School of Molecular Medicine at Northwell Health
    Northwell Health)

  • Seema G. Amin

    (The Feinstein Institutes for Medical Research at Northwell Health
    Cohen Children’s Medical Center)

  • Tea Tsaava

    (The Feinstein Institutes for Medical Research at Northwell Health)

  • Saher Chaudhry

    (The Feinstein Institutes for Medical Research at Northwell Health)

  • Sara P. Valentino

    (The Feinstein Institutes for Medical Research at Northwell Health)

  • Hannah B. Hoffman

    (Northwell Health)

  • Catherine W. Imossi

    (The Feinstein Institutes for Medical Research at Northwell Health)

  • Meghan E. Addorisio

    (The Feinstein Institutes for Medical Research at Northwell Health)

  • Sergio I. Valdes-Ferrer

    (The Feinstein Institutes for Medical Research at Northwell Health)

  • Sangeeta S. Chavan

    (The Feinstein Institutes for Medical Research at Northwell Health
    Elmezzi Graduate School of Molecular Medicine at Northwell Health)

  • Lionel Blanc

    (Elmezzi Graduate School of Molecular Medicine at Northwell Health
    The Feinstein Institutes for Medical Research at Northwell Health
    The Feinstein Institutes for Medical Research at Northwell Health
    Donald and Barbara Zucker School of Medicine at Hofstra/Northwell)

  • Christopher J. Czura

    (The Feinstein Institutes for Medical Research at Northwell Health)

  • Kevin J. Tracey

    (The Feinstein Institutes for Medical Research at Northwell Health
    Elmezzi Graduate School of Molecular Medicine at Northwell Health)

  • Jared M. Huston

    (The Feinstein Institutes for Medical Research at Northwell Health
    Northwell Health
    Donald and Barbara Zucker School of Medicine at Hofstra/Northwell)

Abstract

Deficiency of coagulation factor VIII in hemophilia A disrupts clotting and prolongs bleeding. While the current mainstay of therapy is infusion of factor VIII concentrates, inhibitor antibodies often render these ineffective. Because preclinical evidence shows electrical vagus nerve stimulation accelerates clotting to reduce hemorrhage without precipitating systemic thrombosis, we reasoned it might reduce bleeding in hemophilia A. Using two different male murine hemorrhage and thrombosis models, we show vagus nerve stimulation bypasses the factor VIII deficiency of hemophilia A to decrease bleeding and accelerate clotting. Vagus nerve stimulation targets acetylcholine-producing T lymphocytes in spleen and α7 nicotinic acetylcholine receptors (α7nAChR) on platelets to increase calcium uptake and enhance alpha granule release. Splenectomy or genetic deletion of T cells or α7nAChR abolishes vagal control of platelet activation, thrombus formation, and bleeding in male mice. Vagus nerve stimulation warrants clinical study as a therapy for coagulation disorders and surgical or traumatic bleeding.

Suggested Citation

  • Carlos E. Bravo-Iñiguez & Jason R. Fritz & Shilpa Shukla & Susmita Sarangi & Dane A. Thompson & Seema G. Amin & Tea Tsaava & Saher Chaudhry & Sara P. Valentino & Hannah B. Hoffman & Catherine W. Imoss, 2023. "Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38505-6
    DOI: 10.1038/s41467-023-38505-6
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    References listed on IDEAS

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