ArticleCardiovascular research2012
Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress.
Article in Cardiovascular research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- Pregnane X Receptor‒4β-Hydroxycholesterol Axis in the Regulation of Overweight- and Obesity-Induced Hypertension.Journal of the American Heart Association · 2022Trial
- Role of the lean body mass and of pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of sunitinib in cancer patients.Investigational new drugs · 2015Trial
- Review
- Gut Microbiota in the Regulation of Intestinal Drug Transporters: Molecular Mechanisms and Pharmacokinetic Implications.International journal of molecular sciences · 2025Review
- Mechanisms and Therapeutic Advances of PXR in Metabolic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Bridging the gap in obesity research: A consensus statement from the European Society for Clinical Investigation.European journal of clinical investigation · 2025Review
- Dysregulation of Lipid Metabolism Serves as A Link Between Alzheimer's and Cardiovascular Disease, As Witnessed in A Cross-Sectional Study.Aging and disease · 2024Article
- Mechanistic Review on the Role of Gut Microbiota in the Pathology of Cardiovascular Diseases.Cardiovascular & hematological disorders drug targets · 2024Review
- Anti-Inflammatory and Antioxidant Activities of Lipophilic Fraction fromInternational journal of molecular sciences · 2023Article
- The Role of Bile Acids in Cardiovascular Diseases: from Mechanisms to Clinical Implications.Aging and disease · 2023Article
- Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- The Influence of Zearalenone on Selected Hemostatic Parameters in Sexually Immature Gilts.Toxins · 2021Article
- Characterization of human pregnane X receptor activators identified from a screening of the Tox21 compound library.Biochemical pharmacology · 2021Article
- Review
- PXR is a target of (-)-epicatechin in skeletal muscle.Heliyon · 2020Article
- Cross-Talk between Gut Microbiota and the Heart: A New Target for the Herbal Medicine Treatment of Heart Failure?Evidence-based complementary and alternative medicine : eCAM · 2020Review
- Non-genomic effects of the Pregnane X Receptor negatively regulate platelet functions, thrombosis and haemostasis.Scientific reports · 2019Article
- Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients.Acta pharmacologica Sinica · 2019Observational
- A human xenobiotic nuclear receptor contributes to nonresponsiveness ofThe Journal of biological chemistry · 2018Article
- Tanshinone IIA Protects Endothelial Cells from H₂O₂-Induced Injuries via PXR Activation.Biomolecules & therapeutics · 2017Article
Corrections and comments
- Commented on by
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsCirculating endogenous, dietary, and foreign chemicals can contribute to vascular dysfunction. The mechanism by which the vasculature protects itself from these chemicals is unknown. This study investigates whether the pregnane X receptor (PXR), the major transcriptional regulator of hepatic drug metabolism and transport that responds to such xenobiotics, mediates vascular protection by co-ordinating a defence gene programme in the vasculature. METHODS AND
resultsPXR was detected in primary human and rat aortic endothelial and smooth muscle cells (SMC) and blood vessels including the human and rat aorta. Metabolic PXR target genes cytochrome P450 3A, 2B, 2C, and glutathione S-transferase mRNA and activity were induced by PXR ligands in rodent and human vascular cells and absent in the aortas from PXR-null mice stimulated in vivo or in rat aortic SMC expressing dominant-negative PXR. Activation of aortic PXR by classical agonists had several protective effects: increased xenobiotic metabolism demonstrated by bioactivation of the pro-drug clopidogrel, which reduced adenosine diphosphate-induced platelet aggregation; increased expression of multidrug resistance protein 1, mediating chemical efflux from the vasculature; and protection from reactive oxygen species-mediated cell death.
conclusionPXR co-ordinately up-regulates drug metabolism, transport, and antioxidant genes to protect the vasculature from endogenous and exogenous insults, thus representing a novel gatekeeper for vascular defence.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.