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

Autor: Bravo-Iñiguez CE; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Fritz JR; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Shukla S; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Department of Pediatric Hematology and Oncology, Cohen Children's Medical Center, Northwell Health, Lake Success, NY, 11040, USA., Sarangi S; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Department of Pediatric Hematology and Oncology, Cohen Children's Medical Center, Northwell Health, Lake Success, NY, 11040, USA., Thompson DA; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Department of Surgery, Northwell Health, 300 Community Drive, Manhasset, NY, 11030, USA., Amin SG; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Department of Pediatric Hematology and Oncology, Cohen Children's Medical Center, Northwell Health, Lake Success, NY, 11040, USA., Tsaava T; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Chaudhry S; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Valentino SP; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Hoffman HB; Department of Surgery, Northwell Health, 300 Community Drive, Manhasset, NY, 11030, USA., Imossi CW; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Addorisio ME; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Valdes-Ferrer SI; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Chavan SS; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Blanc L; Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Institute of Molecular Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Departments of Molecular Medicine and Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra Boulevard, Hempstead, NY, 11549, USA., Czura CJ; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Tracey KJ; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.; Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA., Huston JM; Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA. jhuston@northwell.edu.; Department of Surgery, Northwell Health, 300 Community Drive, Manhasset, NY, 11030, USA. jhuston@northwell.edu.; Department of Science Education, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra Boulevard, Hempstead, NY, 11549, USA. jhuston@northwell.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jun 01; Vol. 14 (1), pp. 3122. Date of Electronic Publication: 2023 Jun 01.
DOI: 10.1038/s41467-023-38505-6
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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