Anagrelide alleviates myocardial ischaemia–reperfusion injury by inhibiting reticulated platelets

Abstract

Ischaemia–reperfusion injury (IRI) has been a major challenge during acute coronary syndrome (ACS) with reperfusion therapy. But despite consistent therapeutic improvements in terms of optimized reperfusion strategies and novel antithrombotic medications, IRI still remains highly prevalent. Platelets play a pivotal role in the IRI. Expression ofreticulated platelets (RPs), is found among patients with ACS, which is associated with increased activity and contributes to an impaired response to antiplatelet drugs. RPs might play a more important role in IRI than mature platelets, regarded as a potential therapeutic target for myocardial IRI. Anagrelide, an antithrombopoietic drug indicating for essential thrombocythemia, decreases newly formed platelets by inhibiting the proliferation and differentiation of megakaryocytes in bone marrow. We hypothesize that RPs play a major role in platelet-mediated IRI and that anagrelide alleviates IRI primarily by reducing the number of RPs in the peripheral circulation. To investigate this hypothesis, we have designed animal experiments and clinical trials. Ultimately, we have thoroughly examined potential limitations in confirming this hypothesis and have put forth strategies to effectively address and mitigate these challenges.