Cardiometabolic diseases lead to vascular complications, which cause increasing morbidity and mortality worldwide. The underlying mechanisms are multifactorial and complex but may involve altered purinergic signaling that significantly contributes to cardiovascular dysfunction. Ticagrelor is a successful purinergic drug directly targeting ADP-mediated P2Y₁₂R signaling for platelet aggregation and is widely used in patients with acute coronary syndrome. In addition, ticagrelor can target red blood cells (RBCs) to release ATP and inhibit adenosine uptake by RBCs, which subsequently activate purinergic signaling. This involvement in purinergic signaling may allow ticagrelor to mediate pleiotropic effects and contribute to the beneficial cardiovascular outcomes observed in clinical studies. Recent studies established a novel function of RBCs that RBCs act as disease mediators for the development of cardiovascular complications in type 2 diabetes (T2D). RBC-released ATP is defective in T2D, which has implication for induction of vascular dysfunction by dysregulating purinergic signaling. Ticagrelor might target RBCs and restore the bioavailability of ATP and adenosine thereby attenuating cardiovascular complications. The present perspective discusses the pleiotropic effect of ticagrelor with a focus on the possibility of ticagrelor for the treatment of cardiometabolic complications by targeting RBCs and initiating purinergic activation. A better understanding of the proposed cardiometabolic effects could support novel clinical indications for ticagrelor application.

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替卡格雷：针对红细胞介导的嘌呤能信号传导的抗代谢药物？

心脏代谢疾病会导致血管并发症，从而导致全球发病率和死亡率上升。潜在的机制是多因素的和复杂的，但可能涉及嘌呤能信号转导的改变，这明显导致心血管功能障碍。替卡格雷（Ticagrelor）是直接针对ADP介导的P2Y ₁₂的成功的嘌呤药R信号用于血小板聚集，广泛用于急性冠状动脉综合征患者。此外，替卡格雷可靶向红细胞（RBC）释放ATP并抑制RBC吸收腺苷，随后激活嘌呤能信号传导。嘌呤能信号的这种参与可能使替卡格雷能够介导多效性作用，并有助于临床研究中观察到的有益心血管结果。最近的研究建立了RBC的新功能，即RBC充当2型糖尿病（T2D）心血管并发症发展的疾病介质。RBC释放的ATP在T2D中有缺陷，这暗示着通过嘌呤能信号传导的失调来诱导血管功能障碍。替卡格雷可能会靶向红细胞并恢复ATP和腺苷的生物利用度，从而减轻心血管并发症。本观点讨论了替卡格雷的多效性作用，重点在于替卡格雷通过靶向RBC和启动嘌呤能激活来治疗心脏代谢并发症的可能性。对拟议的心脏代谢作用的更好理解可以支持替卡格雷的新临床适应症。