A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F20%3A00524906" target="_blank" >RIV/67985823:_____/20:00524906 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1016/j.cell.2020.02.016" target="_blank" >https://doi.org/10.1016/j.cell.2020.02.016</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cell.2020.02.016" target="_blank" >10.1016/j.cell.2020.02.016</a>
Alternative languages
Result language
angličtina
Original language name
A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors
Original language description
Using untargeted metabolomics (n = 1,162 subjects), the plasma metabolite (m/z = 265.1188) phenylacetylglutamine (PAGln) was discovered and then shown in an independent cohort (n = 4,000 subjects) to be associated with cardiovascular disease (CVD) and incident major adverse cardiovascular events (myocardial infarction, stroke, or death). A gut microbiota-derived metabolite, PAGln, was shown to enhance platelet activation-related phenotypes and thrombosis potential in whole blood, isolated platelets, and animal models of arterial injury. Functional and genetic engineering studies with human commensals, coupled with microbial colonization of germ-free mice, showed the microbial porA gene facilitates dietary phenylalanine conversion into phenylacetic acid, with subsequent host generation of PAGln and phenylacetylglycine (PAGly) fostering platelet responsiveness and thrombosis potential. Both gain- and loss-of-function studies employing genetic and pharmacological tools reveal PAGln mediates cellular events through G-protein coupled receptors, including alpha 2A, alpha 2B, and beta 2-adrenergic receptors. PAGln thus represents a new CVD-promoting gut microbiota-dependent metabolite that signals via adrenergic receptors.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell
ISSN
0092-8674
e-ISSN
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Volume of the periodical
180
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
862-877
UT code for WoS article
000519189800008
EID of the result in the Scopus database
2-s2.0-85080144111