PMID- 35258452
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20220429
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 11
DP  - 2022 Mar 8
TI  - Gut microbiota induces high platelet response in patients with ST segment 
      elevation myocardial infarction after ticagrelor treatment.
LID - 10.7554/eLife.70240 [doi]
LID - e70240
AB  - BACKGROUND: 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. METHODS: 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 (ABCB1) 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. RESULTS: 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. CONCLUSIONS: 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. FUNDING: NSFC 82170297 
      and 82070300 from the National Natural Science Foundation of China.
CI  - (c) 2022, Zhang et al.
FAU - Zhang, Xi
AU  - Zhang X
AD  - Department of Cardiology and Cardiovascular Research Institute of PLA, General 
      Hospital of Northern Theater Command, Shenyang, China.
AD  - Department of Cardiology, Shengjing Hospital of China Medical University, 
      Shenyang, China.
FAU - Zhang, Xiaolin
AU  - Zhang X
AD  - Department of Cardiology and Cardiovascular Research Institute of PLA, General 
      Hospital of Northern Theater Command, Shenyang, China.
FAU - Tong, Fangnian
AU  - Tong F
AD  - Department of Cardiology and Cardiovascular Research Institute of PLA, General 
      Hospital of Northern Theater Command, Shenyang, China.
FAU - Cai, Yi
AU  - Cai Y
AD  - Department of Cardiology and Cardiovascular Research Institute of PLA, General 
      Hospital of Northern Theater Command, Shenyang, China.
FAU - Zhang, Yujie
AU  - Zhang Y
AD  - Department of Cardiology and Cardiovascular Research Institute of PLA, General 
      Hospital of Northern Theater Command, Shenyang, China.
FAU - Song, Haixu
AU  - Song H
AD  - Department of Cardiology and Cardiovascular Research Institute of PLA, General 
      Hospital of Northern Theater Command, Shenyang, China.
FAU - Tian, Xiaoxiang
AU  - Tian X
AD  - Department of Cardiology and Cardiovascular Research Institute of PLA, General 
      Hospital of Northern Theater Command, Shenyang, China.
FAU - Yan, Chenghui
AU  - Yan C
AD  - Department of Cardiology and Cardiovascular Research Institute of PLA, General 
      Hospital of Northern Theater Command, Shenyang, China.
FAU - Han, Yaling
AU  - Han Y
AUID- ORCID: 0000-0003-4569-6737
AD  - Department of Cardiology and Cardiovascular Research Institute of PLA, General 
      Hospital of Northern Theater Command, Shenyang, China.
AD  - Department of Cardiology, Shengjing Hospital of China Medical University, 
      Shenyang, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220308
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - GLH0314RVC (Ticagrelor)
SB  - IM
MH  - Animals
MH  - Dysbiosis/drug therapy
MH  - *Gastrointestinal Microbiome
MH  - Humans
MH  - Mice
MH  - *Percutaneous Coronary Intervention
MH  - Platelet Aggregation Inhibitors/pharmacokinetics/therapeutic use
MH  - *ST Elevation Myocardial Infarction/drug therapy
MH  - Ticagrelor/therapeutic use
MH  - Treatment Outcome
PMC - PMC8903831
OTO - NOTNLM
OT  - coronary heart disease
OT  - gut microbiota
OT  - high platelet reactivity
OT  - human
OT  - infectious disease
OT  - medicine
OT  - microbiology
OT  - ticagrelor
COIS- XZ, XZ, FT, YC, YZ, HS, XT, CY, YH No competing interests declared
EDAT- 2022/03/09 06:00
MHDA- 2022/04/30 06:00
PMCR- 2022/03/08
CRDT- 2022/03/08 12:21
PHST- 2021/05/11 00:00 [received]
PHST- 2022/02/23 00:00 [accepted]
PHST- 2022/03/08 12:21 [entrez]
PHST- 2022/03/09 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2022/03/08 00:00 [pmc-release]
AID - 70240 [pii]
AID - 10.7554/eLife.70240 [doi]
PST - epublish
SO  - Elife. 2022 Mar 8;11:e70240. doi: 10.7554/eLife.70240.