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.
Nat Commun. 2023 Jun 1;14(1):3122. doi: 10.1038/s41467-023-38505-6.
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.
血友病 A 患者凝血因子 VIII 缺乏会破坏凝血过程并延长出血时间。目前的主要治疗方法是输注凝血因子 VIII 浓缩物，但抑制剂抗体常常使其无效。由于临床前证据表明电刺激迷走神经可以加速凝血以减少出血而不会引发全身性血栓形成，我们推测它可能减少血友病 A 的出血。我们使用两种不同的雄性小鼠出血和血栓形成模型表明，迷走神经刺激可绕过血友病 A 的因子 VIII 缺乏，以减少出血并加速凝血。迷走神经刺激靶向脾脏中产生乙酰胆碱的 T 淋巴细胞和血小板上的α7 烟碱型乙酰胆碱受体 (α7nAChR)，以增加钙摄取并增强α颗粒释放。脾切除术或 T 细胞或 α7nAChR 的基因缺失会消除迷走神经对雄性小鼠血小板活化、血栓形成和出血的控制。迷走神经刺激作为治疗凝血障碍和手术或创伤性出血的一种疗法值得临床研究。
Zotero 插件
