Mitochondrial mitophagy protection combining rivaroxaban and aspirin in high glucose-exposed human coronary artery endothelial cell. An in vitro study

利伐沙班和阿司匹林联合对高糖暴露的人冠状动脉内皮细胞线粒体线粒体自噬的保护作用。一项体外研究

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作者:Khaoula Zekri-Nechar, José Javier Zamorano-León, Mercedes Cortina-Gredilla, Ana López-de-Andrés, Rodrigo Jiménez-García, Carlos Navarro-Cuellar, Antonio López-Farré, Carlos Hugo Martínez-Martínez

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.

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).

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.

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.

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