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 (p < .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 (p < .01). Rivaroxaban 100 mg/ml+25-OHC increased the VE-cadherin expression in endothelium as compared to 25-OHC (p < .05). CONCLUSION: Our finding suggests that rivaroxaban may restore the endothelial barrier and inhibit the inflammatory activation caused by oxysterol in vitro.
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 (p < .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 (p < .01). Rivaroxaban 100 mg/ml+25-OHC increased the VE-cadherin expression in endothelium as compared to 25-OHC (p < .05). CONCLUSION: Our finding suggests that rivaroxaban may restore the endothelial barrier and inhibit the inflammatory activation caused by oxysterol in vitro.
Authors: Marcelo Sanmartín; Sergi Bellmunt; Juan Cosín-Sales; Xavier García-Moll; Antoni Riera-Mestre; Manuel Almendro-Delia; José Luis Hernández; Francisco Lozano; Pilar Mazón; Carmen Suarez Fernández Journal: Expert Rev Clin Pharmacol Date: 2019-07-09 Impact factor: 5.045
Authors: Peter Ellinghaus; Elisabeth Perzborn; Peter Hauenschild; Christoph Gerdes; Stefan Heitmeier; Mayken Visser; Holger Summer; Volker Laux Journal: Thromb Res Date: 2016-04-16 Impact factor: 3.944
Authors: F Luchetti; R Crinelli; E Cesarini; B Canonico; L Guidi; C Zerbinati; G Di Sario; L Zamai; M Magnani; S Papa; L Iuliano Journal: Redox Biol Date: 2017-07-29 Impact factor: 11.799
Authors: Stefan Stojkovic; Christoph Kaun; Jose Basilio; Sabine Rauscher; Lena Hell; Konstantin A Krychtiuk; Cornelia Bonstingl; Rainer de Martin; Marion Gröger; Cihan Ay; Wolfgang Holnthoner; Wolfgang Eppel; Christoph Neumayer; Ihor Huk; Kurt Huber; Svitlana Demyanets; Johann Wojta Journal: Sci Rep Date: 2016-05-04 Impact factor: 4.379