Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, PR China; Hubei Key Laboratory of Cardiology, Wuhan, PR China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, PR China; Hubei Key Laboratory of Cardiology, Wuhan, PR China.
Biochem Biophys Res Commun. 2019 May 21;513(1):99-104. doi: 10.1016/j.bbrc.2019.03.160. Epub 2019 Mar 30.
After myocardial infarction (MI), increased platelet number and size are inversely related to the outcomes of patients. Our previous study confirmed an excessive thrombopoiesis taking place in the bone marrow after MI. However, the mechanisms remain unknown. It has been reported that the sympathetic stimulation by noise or exercise can promote megakaryocyte (MK) producing platelets which is mediated by α2-adrenoceptor. Here, using whole-mount staining combined with western blotting and ELISA assay, we vividly showed an activation of the bone marrow sympathetic nervous system (SNS) after MI. Interestingly, we observed a direct spatial attachment between MKs and the sympathetic nerves. The administration of α-adrenoceptor antagonist, phentolamine or prazosin, could effectively attenuate post-MI MK cellularity and maturity, and alter the distribution of MK away from the bone marrow vessels. Surprisingly, the antagonists did not suppress the final stage of platelet formation. MI mice treated with phentolamine or prazosin showed elevating circulating platelets comparable as those treated with PBS as the control. Together, this study demonstrated that the activation of bone marrow SNS after MI regulates megakaryocyte expansion but not platelet production. Therefore, targeting sympathetic activation might become a novel approach for controlling post-MI bone marrow MK development, but other approaches are still needed to effectively reduce the platelet numbers.
心肌梗死后（MI），血小板数量和大小的增加与患者的预后呈负相关。我们之前的研究证实，MI 后骨髓中存在过度的血小板生成。然而，其机制尚不清楚。有报道称，噪音或运动引起的交感神经刺激可促进巨核细胞（MK）产生血小板，这是由α2-肾上腺素受体介导的。在这里，我们使用全骨髓染色结合 Western blot 和 ELISA 检测，生动地显示了 MI 后骨髓交感神经系统（SNS）的激活。有趣的是，我们观察到 MK 与交感神经之间存在直接的空间附着。α-肾上腺素受体拮抗剂苯肾上腺素或哌唑嗪的给药可有效减弱 MI 后 MK 的细胞活力和成熟度，并改变 MK 从骨髓血管的分布。令人惊讶的是，拮抗剂并没有抑制血小板形成的最后阶段。用苯肾上腺素或哌唑嗪治疗的 MI 小鼠的循环血小板数量升高，与作为对照的 PBS 治疗组相当。总之，这项研究表明，MI 后骨髓 SNS 的激活调节巨核细胞的扩增，但不调节血小板的生成。因此，靶向交感神经激活可能成为控制 MI 后骨髓 MK 发育的新方法，但仍需要其他方法来有效降低血小板数量。
