Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells

by Selleckchem | Oct 08 2023

Background: We evaluated the efficacy of the factor Xa inhibitor rivaroxaban on the differentiation ability of vascular endothelial progenitor cells (EPCs), which play roles in vascular injury repair and atherogenesis. Antithrombotic treatment in patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is challenging, and current guidelines recommend oral anticoagulant monotherapy 1 year or more after PCI. However, biological evidence of the pharmacological effects of anticoagulants is insufficient.

Methods: EPC colony-forming assays were performed using peripheral blood-derived CD34-positive cells from healthy volunteers. Adhesion and tube formation of cultured EPCs were assessed in human umbilical cord-derived CD34-positive cells. Endothelial cell surface markers were assessed using flow cytometry, and Akt and endothelial nitric oxide synthase (eNOS) phosphorylation were examined using western blot analysis of EPCs. Adhesion, tube formation and endothelial cell surface marker expression was observed in EPCs transfected with small interfering RNA (siRNA) against protease-activated receptor (PAR)-2. Finally, EPC behaviors were assessed in patients with atrial fibrillation undergoing PCI in whom warfarin was changed to rivaroxaban.

Results: Rivaroxaban increased the number of large EPC colonies and increased the bioactivities of EPCs, including adhesion and tube formation. Rivaroxaban also increased vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, Tie-2, and E-selectin expression as well as Akt and eNOS phosphorylation. PAR-2 knockdown increased the bioactivities of EPCs and endothelial cell surface marker expression. Patients in whom the number of large colonies increased after switching to rivaroxaban showed better vascular repair.

Conclusions: Rivaroxaban increased the differentiation ability of EPCs, leading to potential advantages in the treatment of coronary artery disease.

Comments:

The study you described evaluated the effects of the factor Xa inhibitor rivaroxaban on the differentiation ability of vascular endothelial progenitor cells (EPCs). EPCs are involved in repairing vascular injuries and the development of atherosclerosis. The aim was to investigate the potential pharmacological effects of anticoagulants, specifically rivaroxaban, in patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI).

The methods employed in the study involved conducting EPC colony-forming assays using CD34-positive cells derived from healthy volunteers. The researchers assessed the adhesion and tube formation of cultured EPCs derived from human umbilical cord CD34-positive cells. Flow cytometry was used to analyze endothelial cell surface markers, while western blot analysis was performed to examine Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in EPCs. Additionally, the researchers transfected EPCs with small interfering RNA (siRNA) targeting protease-activated receptor (PAR)-2 to observe its effects on adhesion, tube formation, and endothelial cell surface marker expression. Lastly, the study assessed the behaviors of EPCs in patients with atrial fibrillation undergoing PCI after switching from warfarin to rivaroxaban.

The results of the study demonstrated that rivaroxaban increased the number of large EPC colonies and enhanced the bioactivities of EPCs, such as adhesion and tube formation. Rivaroxaban also upregulated the expression of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, Tie-2, and E-selectin, as well as Akt and eNOS phosphorylation in EPCs. Knockdown of PAR-2 resulted in increased bioactivities of EPCs and endothelial cell surface marker expression. Notably, patients who showed an increase in the number of large colonies after switching to rivaroxaban exhibited improved vascular repair.

In conclusion, the study suggests that rivaroxaban enhances the differentiation ability of EPCs, which may have potential benefits in the treatment of coronary artery disease. These findings contribute to the understanding of the pharmacological effects of anticoagulants and provide insights into the potential therapeutic advantages of rivaroxaban in patients with atrial fibrillation undergoing PCI.