دورية أكاديمية
Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk
| العنوان: | Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk |
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| المؤلفون: | Zhu, Weifei, Gregory, Jill C., Org, Elin, Buffa, Jennifer A., Gupta, Nilaksh, Wang, Zeneng, Li, Lin, Fu, Xiaoming, Wu, Yuping, Mehrabian, Margarete, Sartor, R. Balfour, McIntyre, Thomas M., Silverstein, Roy L., Tang, W.H. Wilson, Didonato, Joseph A., Brown, J. Mark, Lusis, Aldons J., Hazen, Stanley L. |
| المصدر: | Cell, 165(1) |
| سنة النشر: | 2016 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Carotid Artery Injuries, Calcium, Mice, Choline, Animals, Gastrointestinal Microbiome, Female, Ferric Compounds, Humans, Diet, Methylamines, Inbred C57BL, Chlorides, Thrombosis, Germ-Free Life, Cecum, Blood Platelets |
| الوصف: | Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (N>4000) independently predicted incident (3 yr) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced submaximal stimulus-dependent platelet activation from multiple agonists through augmented Ca2+ release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation, collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential, and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/vrx4-j764Test; https://cdr.lib.unc.edu/downloads/3j333690v?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/3j333690vTest |
| DOI: | 10.17615/vrx4-j764 |
| الإتاحة: | https://doi.org/10.17615/vrx4-j764Test https://cdr.lib.unc.edu/downloads/3j333690v?file=thumbnailTest https://cdr.lib.unc.edu/downloads/3j333690vTest |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.87D045CC |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/vrx4-j764 |
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