Rivaroxaban Protects from the Oxysterol-induced Damage and Inflammatory Activation of the Vascular Endothelium

Overview

Journal Tissue Barriers

Specialties Anatomy & Histology
Biology
Physiology

Date 2021 Jul 29

PMID 34323663

Citations 4

Authors

Paulina Gorzelak-Pabis

Marlena Broncel

Katarzyna Wojdan

Adrian Gajewski

Maciej Chalubinski

Mateusz Gawrysiak

Ewelina Wozniak

Affiliations

Soon will be listed here.

Abstract

Background: Rivaroxaban is one of the direct factor Xa inhibitors. Its function in the inactivated coagulation cascade is unclear. The aim of the study was to assess the effect of rivaroxaban on the endothelial integrity and inflammatory properties of endothelial cells stimulated by 25-hydroxycholesterol (25-OHC).

Methods: HUVECs were stimulated with 25-OHC, rivaroxaban and 25-OHC+ rivaroxaban. HUVEC integrity and permeability were measured using the xCELLigence system and paracellular flux assay. The mRNA expression of tissue factor, ICAM-1, VEGF, IL-33, MCP-1, TNF-α was analyzed in the real-time PCR. Apoptosis and viability were measured by flow cytometry. The VEGF protein concentration was assessed by ELISA. The confocal microscope was used to evaluate the expression of VE-cadherin in endothelial cells.

Results: 25-OHC decreased endothelial cell integrity and increased the mRNA expression of IL-33, tissue factor, ICAM-1, MCP-1, VEGF, TNF-α as compared to unstimulated controls. Following the stimulation with rivaroxaban, HUVEC restored integrity disrupted by 25-OHC ( < .01). In HUVECs pre-stimulated with oxysterol, rivaroxaban decreased mRNA expression of IL-33, TNF-α, chemokines MCP-1, ICAM-1, VEGF and tissue factor ( < .01). Rivaroxaban 100 mg/ml+25-OHC increased the VE-cadherin expression in endothelium as compared to 25-OHC ( < .05).

Conclusion: Our finding suggests that rivaroxaban may restore the endothelial barrier and inhibit the inflammatory activation caused by oxysterol .

Citing Articles

25-Hydroxycholesterol in health and diseases.

Nguyen C, Saint-Pol J, Dib S, Pot C, Gosselet F J Lipid Res. 2023; 65(1):100486.

PMID: 38104944 PMC: 10823077. DOI: 10.1016/j.jlr.2023.100486.

Distinct pleiotropic effects of direct oral anticoagulants on cultured endothelial cells: a comprehensive review.

Atzemian N, Kareli D, Ragia G, Manolopoulos V Front Pharmacol. 2023; 14:1244098.

PMID: 37841935 PMC: 10576449. DOI: 10.3389/fphar.2023.1244098.

Endothelial cell dysfunction: Implications for the pathogenesis of peripheral artery disease.

Kavurma M, Bursill C, Stanley C, Passam F, Cartland S, Patel S Front Cardiovasc Med. 2022; 9:1054576.

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Delivery of rivaroxaban and chitosan rapamycin microparticle with dual antithrombosis and antiproliferation functions inhibits venous neointimal hyperplasia.

Sun P, Wu H, He H, Zhang L, Liu Y, Zhang C Drug Deliv. 2022; 29(1):1994-2001.

PMID: 35762638 PMC: 9246098. DOI: 10.1080/10717544.2022.2092240.

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