PURPOSE: Combination of Rivaroxaban plus Aspirin improved cardiovascular outcome in patients with stable cardiovascular disease. The aim was to determine if Rivaroxaban and acetylsalicylic acid alone or in combination may protect mitochondrial mitophagy in human coronary artery endothelial cells (HCAEC) exposed to D-glucose. METHODS: HCAEC were incubated under different conditions: 5 mmol/L glucose D-glucose (control), 30 mmol/L D-Glucose with and without 50 nmol/L Rivaroxaban (Rivaroxaban), 0.33 mmol/L ASA (ASA) or Rivaroxaban (12.5 nmol/L)+ASA (0.33 mmol/L; (Riva+ASA). RESULTS: HCAEC incubated with D-glucose showed an increased Factor Xa expression. The mitochondrial content of Pink-1 and Parkin were significantly reduced in high glucose-incubated HCAEC compared to control. Rivaroxaban+ASA significantly increased the mitochondrial content of Pink-1 and Parkin, and the mitochondrial membrane potential compared to D-Glucose group. Both ASA alone and Riva+ASA reduced reactive oxygen species (ROS) and tissue factor production induced by high glucose exposure. CONCLUSION: Under high glucose condition combining Rivaroxaban+ASA increased the mitochondrial content of Pink-1 and Parkin, restored mitochondria membrane potential and reduced ROS and tissue factor expression in HCAEC. It suggests potential effects induced by dual use of Rivaroxaban and ASA on the coronary endothelium subjected to high glucose condition.
PURPOSE: Combination of Rivaroxaban plus Aspirin improved cardiovascular outcome in patients with stable cardiovascular disease. The aim was to determine if Rivaroxaban and acetylsalicylic acid alone or in combination may protect mitochondrial mitophagy in human coronary artery endothelial cells (HCAEC) exposed to D-glucose. METHODS: HCAEC were incubated under different conditions: 5 mmol/L glucose D-glucose (control), 30 mmol/L D-Glucose with and without 50 nmol/L Rivaroxaban (Rivaroxaban), 0.33 mmol/L ASA (ASA) or Rivaroxaban (12.5 nmol/L)+ASA (0.33 mmol/L; (Riva+ASA). RESULTS: HCAEC incubated with D-glucose showed an increased Factor Xa expression. The mitochondrial content of Pink-1 and Parkin were significantly reduced in high glucose-incubated HCAEC compared to control. Rivaroxaban+ASA significantly increased the mitochondrial content of Pink-1 and Parkin, and the mitochondrial membrane potential compared to D-Glucose group. Both ASA alone and Riva+ASA reduced reactive oxygen species (ROS) and tissue factor production induced by high glucose exposure. CONCLUSION: Under high glucose condition combining Rivaroxaban+ASA increased the mitochondrial content of Pink-1 and Parkin, restored mitochondria membrane potential and reduced ROS and tissue factor expression in HCAEC. It suggests potential effects induced by dual use of Rivaroxaban and ASA on the coronary endothelium subjected to high glucose condition.
Authors: John W Eikelboom; Stuart J Connolly; Jackie Bosch; Gilles R Dagenais; Robert G Hart; Olga Shestakovska; Rafael Diaz; Marco Alings; Eva M Lonn; Sonia S Anand; Petr Widimsky; Masatsugu Hori; Alvaro Avezum; Leopoldo S Piegas; Kelley R H Branch; Jeffrey Probstfield; Deepak L Bhatt; Jun Zhu; Yan Liang; Aldo P Maggioni; Patricio Lopez-Jaramillo; Martin O'Donnell; Ajay K Kakkar; Keith A A Fox; Alexander N Parkhomenko; Georg Ertl; Stefan Störk; Matyas Keltai; Lars Ryden; Nana Pogosova; Antonio L Dans; Fernando Lanas; Patrick J Commerford; Christian Torp-Pedersen; Tomek J Guzik; Peter B Verhamme; Dragos Vinereanu; Jae-Hyung Kim; Andrew M Tonkin; Basil S Lewis; Camilo Felix; Khalid Yusoff; P Gabriel Steg; Kaj P Metsarinne; Nancy Cook Bruns; Frank Misselwitz; Edmond Chen; Darryl Leong; Salim Yusuf Journal: N Engl J Med Date: 2017-08-27 Impact factor: 91.245
Authors: Gala Freixer; Khaoula Zekri-Nechar; José J Zamorano-León; Carlos Hugo-Martínez; Nora V Butta; Elena Monzón; María-José Recio; Manel Giner; Antonio López-Farré Journal: Platelets Date: 2020-10-28 Impact factor: 3.862