Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
November 20, 2019Scientific ReportsOpen Access

Non-genomic effects of the Pregnane X Receptor negatively regulate platelet functions, thrombosis and haemostasis

View Full Paper
Ask AI
Bookmark
Share

Key result

Treatment with PXR ligands SR12813 and rifampicin acutely inhibited platelet aggregation, granule secretion, and thrombus formation both in vitro and in vivo by down-regulating Src-family kinase signaling.

Why the study?

Given the presence of pregnane X receptor (PXR) in the vasculature, anti-atherosclerotic effects of its ligands, and the role of platelets in atherosclerosis, the study investigated PXR expression in platelets and the ability of its ligands to modulate platelet activation.

Do PXR ligands inhibit platelet function and thrombus formation in human platelets and humanised PXR transgenic mice?

Population

Human platelets and humanised PXR transgenic mice

Comparison

Treatment with PXR ligands vs control

Design

Preclinical in vitro and in vivo laboratory study

Authors

GFGagan D. FloraUniversity of IowaKSKhaled A. SahliSecurity Forces HospitalPSParvathy SasikumarHammersmith Hospital

Discussion

Loading...

Member takes

Implication

PXR ligands may modulate platelet activation; leaves open any role in human atherosclerosis prevention.

Structured PICO

Do PXR ligands inhibit platelet function and thrombus formation in human platelets and humanised PXR transgenic mice?

P
Population
In vitro and in vivo preclinical study using blood from healthy aspirin-free volunteers and humanised PXR transgenic mice to evaluate platelet function.
I
Intervention
PXR ligands (including human-specific ligand SR12813)
O
Outcome
Platelet function (aggregation, granule secretion, adhesion, spreading) and thrombus formationsurrogate

PXR ligands exert acute, non-genomic anti-thrombotic effects by inhibiting platelet function via Src-family kinases, suggesting potential cardioprotective benefits.

Limitations

  • High micromolar concentrations of PXR ligands were required to elicit acute biological effects, which are higher than typical circulating plasma concentrations.
  • The tail-bleeding assay takes into account both platelet function and coagulation, so effects on coagulation cannot be excluded.
  • The exact molecular basis of PXR interaction with SFKs requires further exploration.

Cite This Study

Flora et al. (2019) studied Healthy volunteers (in vitro) and humanised PXR transgenic mice (in vivo). PXR ligands (SR12813 and rifampicin) vs. Vehicle control (DMSO) was evaluated on Platelet aggregation, granule secretion, and thrombus formation. Treatment with PXR ligands SR12813 and rifampicin acutely inhibited platelet aggregation, granule secretion, and thrombus formation both in vitro and in vivo by down-regulating Src-family kinase signaling.

synapsesocial.com/papers/6a9e46464a8b3000dc6aad7ahttps://doi.org/10.1038/s41598-019-53218-x
View Full Paper
Ask AI
Bookmark
Share

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Antiplatelet Actions of Statins and Fibrates Are Mediated by PPARs2009 · 130 citations
  2. 2PPARγ agonists negatively regulate αIIbβ3 integrin outside‐in signaling and platelet function through up‐regulation of protein kinase A activity2016 · 29 citations
  3. 3Src family kinases: at the forefront of platelet activation2014 · 302 citations
  4. 4Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets2007 · 82 citations
  5. 5Why Do We Use 600 mg of Rifampicin in Tuberculosis Treatment?2011 · 245 citations