Department of Cardiology, Hainan General Hospital, Haikou, People's Republic of China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, People's Republic of China.
Sci Rep. 2021 Mar 22;11(1):6580. doi: 10.1038/s41598-021-85950-8.
Trimethylamine-N-oxide (TMAO) can activate platelets and increase thrombosis risk in clinical and experimental models. Meanwhile, the patients with coronary artery disease have higher serum TMAO level. However, it remains unknown whether Clopidogrel Resistance (CR) could be attributed to TMAO. The present study aimed investigate the effects of TMAO on clopidogrel in ischemia and reperfusion (IR) model in rats. Clopidogrel could (1) promote the production of platelets, induce an increase in the platelet-larger cell ratio; (2) prolong the tail bleeding time; (3) reduce platelet aggregation function, induced by ADP, and alleviate myocardial thrombus burden. TMAO could partially offset the effects of clopidogrel and induce CR. Thus, the present study demonstrated that circulating TMAO could reduce the inhibitory effects of clopidogrel on platelet aggregation. TMAO may be a potential mediator of clopidogrel resistance.
三甲基胺 N-氧化物（TMAO）可激活血小板并增加临床和实验模型中的血栓形成风险。同时，冠心病患者的血清 TMAO 水平较高。然而，目前尚不清楚氯吡格雷抵抗（CR）是否归因于 TMAO。本研究旨在探讨 TMAO 对大鼠缺血再灌注（IR）模型中氯吡格雷的作用。氯吡格雷可以：（1）促进血小板的产生，诱导血小板-大细胞比值增加；（2）延长尾部出血时间；（3）降低 ADP 诱导的血小板聚集功能，并减轻心肌血栓负荷。TMAO 可以部分抵消氯吡格雷的作用，诱导 CR。因此，本研究表明循环 TMAO 可降低氯吡格雷对血小板聚集的抑制作用。TMAO 可能是氯吡格雷抵抗的潜在介质。
