Department of Cardiology and Cardiovascular Research Institute of PLA, General Hospital of Northern Theater Command, Shenyang, China.
Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
Elife. 2022 Mar 8;11:e70240. doi: 10.7554/eLife.70240.
Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear.
To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokinetic assessment result showed that the plasma concentrations of ticagrelor and its metabolism production, AR-C124910XX, were lower in HPR patients than controls. Further single nucloetide polymorphism (SNP) analysis identified that there is no difference in ATP binding cassette subfamily B member 1 () gene expression between the NPR group and the HPR group. Metagenomic and metabolomic analyses of fecal samples showed that HPR patients had higher microbial richness and diversity. Transplantation of the gut microbiota from HPR donors to microbiota-depleted mice obviously decreased plasma concentration of ticagrelor.
Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with STEMI and support that modify gut microbiota is a potential therapeutic option for STEMI.
Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with ST elevation myocardial infarction (STEMI) and support that modify gut microbiota is a potential therapeutic option for STEMI.
NSFC 82170297 and 82070300 from the National Natural Science Foundation of China.
替格瑞洛是治疗急性 ST 段抬高型心肌梗死（STEMI）的一线药物。然而，约 20%接受替格瑞洛治疗的 STEMI 患者表现出延迟反应，其机制尚不清楚。
为了探讨经皮冠状动脉介入治疗（PCI）后替格瑞洛反应不佳的机制，我们纳入了 65 例高血小板反应性（HPR）患者和 90 例对照（正常血小板反应性 [NPR]）。药代动力学评估结果显示，HPR 患者的替格瑞洛及其代谢产物 AR-C124910XX 血浆浓度低于对照组。进一步的单核苷酸多态性（SNP）分析表明，NPR 组和 HPR 组之间 ABCB1 基因表达无差异。粪便样本的宏基因组和代谢组学分析显示，HPR 患者的微生物丰富度和多样性更高。将 HPR 供体的肠道微生物群移植到微生物群耗竭的小鼠中，明显降低了替格瑞洛的血浆浓度。
我们的研究结果强调，肠道微生物群失调可能是 STEMI 患者替格瑞洛高反应性的重要机制，并支持肠道微生物群调节可能是 STEMI 的潜在治疗选择。
我们的研究结果强调，肠道微生物群失调可能是 STEMI 患者替格瑞洛高反应性的重要机制，并支持肠道微生物群调节可能是 STEMI 的潜在治疗选择。
国家自然科学基金 NSFC 82170297 和 82070300。
