Key result
Rivaroxaban reduced the expression of CYP4F2 and CYP4F2 protein levels in HUVECs, while the expression of transcription factors HNF4α, PXR and CAR was not detected.
Why the study?
Interindividual variability among patients taking rivaroxaban results from hepatic metabolism by CYP 450 enzymes, prompting evaluation of rivaroxaban's impact on CYP4F2 and transcription factor activity.
Rivaroxaban is metabolized by and reduces the expression of CYP4F2 in human endothelial cells, providing insight into its cellular interactions and interindividual variability.
Hypothesis-generating for CYP4F2-mediated rivaroxaban effects in endothelium; prospective studies needed before clinical relevance.
Interindividual variabilities between patients taking the anticoagulant rivaroxaban are a result of hepatic metabolism by CYP 450 enzymes. The objective of this study was to evaluate the impact of rivaroxaban on CYP4F2 and transcription factors’ activity in HUVECs. Rivaroxaban and its metabolites were detected by UPLC-ESI-MS and UPLC-QTOF-MS. CYP4F2, HNF4α, PXR and CAR expressions were determined in HUVECs by qPCR; CYP4F2 protein concentration was determined by ELISA. Rivaroxaban metabolites (M-1, M-2, M-5, M-8, M-10, M-11 and M-18) were detected in endothelial cells’ culture medium. Increasing concentrations of rivaroxaban determined lower 13-docosenamide concentrations. Rivaroxaban and dexamethasone reduced the expression of CYP4F2 when hsa-miR-24-3p—both CYP4F2 expression and CYP4F2 protein levels in HUVECs. The expression of the transcription factors HNF4α, PXR and CAR was not detected in HUVECs.
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Čiapienė et al. (2021) studied this question. Rivaroxaban was evaluated on CYP4F2 and transcription factors' activity in HUVECs. Rivaroxaban reduced the expression of CYP4F2 and CYP4F2 protein levels in HUVECs, while the expression of transcription factors HNF4α, PXR and CAR was not detected.
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