Farnesoid X Receptor and Its Ligands Inhibit the Function of Platelets Article Swipe
Leonardo A. Moraes
,
Amanda J. Unsworth
,
Sakthivel Vaiyapuri
,
Marfoua S. Ali
,
Parvathy Sasikumar
,
Tanya Sage
,
Gagan D. Flora
,
Alexander P. Bye
,
Neline Kriek
,
Emilie Dorchies
,
Olivier Molendi‐Coste
,
David Dombrowicz
,
Bart Staels
,
David Bishop‐Bailey
,
Jonathan M. Gibbins
·
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.1161/atvbaha.116.308093
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.1161/atvbaha.116.308093
Objective— Although initially seemingly paradoxical because of the lack of nucleus, platelets possess many transcription factors that regulate their function through DNA-independent mechanisms. These include the farnesoid X receptor (FXR), a member of the superfamily of ligand-activated transcription factors, that has been identified as a bile acid receptor. In this study, we show that FXR is present in human platelets and FXR ligands, GW4064 and 6α-ethyl-chenodeoxycholic acid, modulate platelet activation nongenomically. Approach and Results— FXR ligands inhibited the activation of platelets in response to stimulation of collagen or thrombin receptors, resulting in diminished intracellular calcium mobilization, secretion, fibrinogen binding, and aggregation. Exposure to FXR ligands also reduced integrin α IIb β 3 outside-in signaling and thereby reduced the ability of platelets to spread and to stimulate clot retraction. FXR function in platelets was found to be associated with the modulation of cyclic guanosine monophosphate levels in platelets and associated downstream inhibitory signaling. Platelets from FXR-deficient mice were refractory to the actions of FXR agonists on platelet function and cyclic nucleotide signaling, firmly linking the nongenomic actions of these ligands to the FXR. Conclusions— This study provides support for the ability of FXR ligands to modulate platelet activation. The atheroprotective effects of GW4064, with its novel antiplatelet effects, indicate FXR as a potential target for the prevention of atherothrombotic disease.
Related Topics
Concepts
Farnesoid X receptor
Platelet
Chemistry
Function (biology)
Receptor
Cell biology
Biochemistry
Internal medicine
Biology
Nuclear receptor
Medicine
Gene
Transcription factor
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1161/atvbaha.116.308093
- https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.116.308093
- OA Status
- bronze
- Cited By
- 32
- References
- 55
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2556571347
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2556571347Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1161/atvbaha.116.308093Digital Object Identifier
- Title
-
Farnesoid X Receptor and Its Ligands Inhibit the Function of PlateletsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2016Year of publication
- Publication date
-
2016-10-06Full publication date if available
- Authors
-
Leonardo A. Moraes, Amanda J. Unsworth, Sakthivel Vaiyapuri, Marfoua S. Ali, Parvathy Sasikumar, Tanya Sage, Gagan D. Flora, Alexander P. Bye, Neline Kriek, Emilie Dorchies, Olivier Molendi‐Coste, David Dombrowicz, Bart Staels, David Bishop‐Bailey, Jonathan M. GibbinsList of authors in order
- Landing page
-
https://doi.org/10.1161/atvbaha.116.308093Publisher landing page
- PDF URL
-
https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.116.308093Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.116.308093Direct OA link when available
- Concepts
-
Farnesoid X receptor, Platelet, Chemistry, Function (biology), Receptor, Cell biology, Biochemistry, Internal medicine, Biology, Nuclear receptor, Medicine, Gene, Transcription factorTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
32Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 2, 2022: 2, 2021: 1, 2020: 2Per-year citation counts (last 5 years)
- References (count)
-
55Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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