Bone marrow sympathetic activation regulates post-myocardial infarction megakaryocyte expansion but not platelet production.

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.