The Effect of Rivaroxaban on CYP4F2 and Transcription Factors’ Activity in HUVECs

Ieva Ciapiene; Vacis Tatarunas; Agne Giedraitiene; Vaidotas Zvikas; Valdas Jakstas; Audrone Veikutiene; Ugne Meskauskaite; Ugne Venckyte; Audrius Pukalskas; Vaiva Lesauskaite

doi:10.3390/app112210851

Applied Sciences (Nov 2021)

The Effect of Rivaroxaban on CYP4F2 and Transcription Factors’ Activity in HUVECs

Ieva Ciapiene,
Vacis Tatarunas,
Agne Giedraitiene,
Vaidotas Zvikas,
Valdas Jakstas,
Audrone Veikutiene,
Ugne Meskauskaite,
Ugne Venckyte,
Audrius Pukalskas,
Vaiva Lesauskaite

Affiliations

Ieva Ciapiene: Institute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT 50103 Kaunas, Lithuania
Vacis Tatarunas: Institute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT 50103 Kaunas, Lithuania
Agne Giedraitiene: Institute of Microbiology and Virology, Lithuanian University of Health Sciences, Eiveniu 4, LT 50161 Kaunas, Lithuania
Vaidotas Zvikas: Institute of Pharmaceutical Technologies, Lithuanian University of Health Sciences, Sukileliu 13, LT 50166 Kaunas, Lithuania
Valdas Jakstas: Institute of Pharmaceutical Technologies, Lithuanian University of Health Sciences, Sukileliu 13, LT 50166 Kaunas, Lithuania
Audrone Veikutiene: Institute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT 50103 Kaunas, Lithuania
Ugne Meskauskaite: Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus 9, LT 44307 Kaunas, Lithuania
Ugne Venckyte: Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus 9, LT 44307 Kaunas, Lithuania
Audrius Pukalskas: Faculty of Chemical Technology, Kaunas University of Technology, Radvilenu 19, LT 50254 Kaunas, Lithuania
Vaiva Lesauskaite: Institute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT 50103 Kaunas, Lithuania

DOI: https://doi.org/10.3390/app112210851
Journal volume & issue: Vol. 11, no. 22
p. 10851

Abstract

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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.

Published in Applied Sciences

ISSN: 2076-3417 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology: Engineering (General). Civil engineering (General); Science: Biology (General); Science: Physics; Science: Chemistry
Website: http://www.mdpi.com/journal/applsci

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