Cargando…
Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells
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 percutan...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236699/ https://www.ncbi.nlm.nih.gov/pubmed/37268884 http://dx.doi.org/10.1186/s12872-023-03318-4 |
_version_ | 1785053001437675520 |
---|---|
author | Sohma, Ryoichi Sakuma, Masashi Obi, Syotaro Nishino, Setsu Inoue, Ken-ichi Kishimoto, Satoko Lu, Tianyang Toyoda, Shigeru Inoue, Teruo |
author_facet | Sohma, Ryoichi Sakuma, Masashi Obi, Syotaro Nishino, Setsu Inoue, Ken-ichi Kishimoto, Satoko Lu, Tianyang Toyoda, Shigeru Inoue, Teruo |
author_sort | Sohma, Ryoichi |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-023-03318-4. |
format | Online Article Text |
id | pubmed-10236699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-102366992023-06-03 Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells Sohma, Ryoichi Sakuma, Masashi Obi, Syotaro Nishino, Setsu Inoue, Ken-ichi Kishimoto, Satoko Lu, Tianyang Toyoda, Shigeru Inoue, Teruo BMC Cardiovasc Disord Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-023-03318-4. BioMed Central 2023-06-02 /pmc/articles/PMC10236699/ /pubmed/37268884 http://dx.doi.org/10.1186/s12872-023-03318-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Sohma, Ryoichi Sakuma, Masashi Obi, Syotaro Nishino, Setsu Inoue, Ken-ichi Kishimoto, Satoko Lu, Tianyang Toyoda, Shigeru Inoue, Teruo Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells |
title | Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells |
title_full | Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells |
title_fullStr | Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells |
title_full_unstemmed | Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells |
title_short | Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells |
title_sort | effects of the factor xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236699/ https://www.ncbi.nlm.nih.gov/pubmed/37268884 http://dx.doi.org/10.1186/s12872-023-03318-4 |
work_keys_str_mv | AT sohmaryoichi effectsofthefactorxainhibitorrivaroxabanonthedifferentiationofendothelialprogenitorcells AT sakumamasashi effectsofthefactorxainhibitorrivaroxabanonthedifferentiationofendothelialprogenitorcells AT obisyotaro effectsofthefactorxainhibitorrivaroxabanonthedifferentiationofendothelialprogenitorcells AT nishinosetsu effectsofthefactorxainhibitorrivaroxabanonthedifferentiationofendothelialprogenitorcells AT inouekenichi effectsofthefactorxainhibitorrivaroxabanonthedifferentiationofendothelialprogenitorcells AT kishimotosatoko effectsofthefactorxainhibitorrivaroxabanonthedifferentiationofendothelialprogenitorcells AT lutianyang effectsofthefactorxainhibitorrivaroxabanonthedifferentiationofendothelialprogenitorcells AT toyodashigeru effectsofthefactorxainhibitorrivaroxabanonthedifferentiationofendothelialprogenitorcells AT inoueteruo effectsofthefactorxainhibitorrivaroxabanonthedifferentiationofendothelialprogenitorcells |