Cohen Haim, Keren-Politansky Anat, Crispel Yonatan, Yanovich Chen, Asayag Keren, Nadir Yona
Thrombosis and Hemostasis Unit, Department of Hematology, Rambam Health Care Campus, Haifa 31096, Israel.
The Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel.
Biology (Basel). 2023 Oct 30;12(11):1388. doi: 10.3390/biology12111388.
Hemophilia A and B induce recurrent bleeding episodes, mainly in skeletal muscles and joints that are in intermittent motion. We have previously demonstrated that intermittent motion contributes to increased degradation of factors VIII and IX. Given that calcium ions are known to enhance factor VIII-von Willebrand factor (vWF) interaction, the present study has investigated the role of these ions on factors VIII and IX in the condition of motion. The effects of calcium ions were assessed using purified proteins via Western blot, factor VIII activity, immunocytochemistry, and in Institute of Cancer Research (ICR) mice with no specific genetic background. Calcium was found to prevent degradation of plasma-derived factor VIII but not that of factor IX, during intermittent motion. Calcium levels in the microcirculation of mouse striated muscles were elevated following movement, enabling prevention of factor VIII degradation in normal physiology. Calcium supplementation in drinking water increased factor VIII levels in blood and striated muscles of ICR mice during movement. calcium ions decrease factor VIII degradation in the condition of motion. Further research on the impact of calcium salt oral supplementation on hemophilia patients is warranted.
甲型和乙型血友病会引发反复出血发作,主要发生在处于间歇性运动的骨骼肌和关节。我们之前已经证明,间歇性运动导致因子VIII和IX的降解增加。鉴于已知钙离子会增强因子VIII与血管性血友病因子(vWF)的相互作用,本研究调查了这些离子在运动状态下对因子VIII和IX的作用。通过蛋白质印迹法、因子VIII活性检测、免疫细胞化学以及在无特定遗传背景的癌症研究所(ICR)小鼠中,使用纯化蛋白评估钙离子的作用。结果发现,在间歇性运动期间,钙离子可防止血浆来源的因子VIII降解,但不能防止因子IX降解。运动后小鼠横纹肌微循环中的钙水平升高,从而在正常生理状态下防止因子VIII降解。在饮用水中补充钙可增加运动期间ICR小鼠血液和横纹肌中的因子VIII水平。钙离子在运动状态下可减少因子VIII降解。有必要进一步研究口服钙盐对血友病患者的影响。