eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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1/2019
vol. 15
 
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abstract:
Basic research

Renin-angiotensin system inhibitor attenuates oxidative stress induced human coronary artery endothelial cell dysfunction via the PI3K/AKT/mTOR pathway

Xuekun Shi, Yuhua Guan, Shaoyan Jiang, Tiandong Li, Bing Sun, Huan Cheng

Arch Med Sci 2019; 15, 1: 152–164
Online publish date: 2018/03/08
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Introduction
The renin-angiotensin system is associated with blood pressure regulation, inflammation, oxidative stress and insulin resistance. It can decrease intracellular oxidative stress. Stimulation with H2O2 leads to increased oxidative stress and activation of the AKT/mTOR pathway. However, the role of renin-angiotensin system inhibitors in oxidative stress-induced endothelial cell dysfunction and H2O2-induced AKT activation remains unclear.

Material and methods
Human coronary artery endothelial cells (HCAECs) were used. The cells were treated with H2O2, captopril, the AKT inhibitor MK-2206, and the AKT activator SC79, either separately, or in combination. p53 and ICAM-1 expression, and p-eNOS, p-Akt and mTOR activation were measured by Western blot. Cell viability was assessed by MTT assay. Levels of reactive oxygen species (ROS) were assayed by flow cytometry. Proliferation was monitored by BrdU labeling, while cell migration and invasion were determined by wound healing and Transwell assays, respectively.

Results
The renin-angiotensin system inhibitor captopril reversed H2O2-induced oxidative stress and apoptosis in HCAECs. Co-treatment with captopril and the AKT inhibitor MK-2206 reduced the H2O2-induced P53 and ICAM-1 protein expression (p < 0.05). The proliferation, migration and invasion of HCAECs were significantly enhanced by co-treatment with captopril and MK-2206 (p < 0.05).

Conclusions
The study revealed the protective effect of captopril against H2O2-induced endothelial cell dysfunction through the AKT/mTOR pathway, and its enhancement of cell survival. These findings provide new insights into the protective effects of captopril and novel therapeutic approaches to treatment of cardiovascular disease.

keywords:

renin-angiotensin system inhibitor, AKT/mTOR pathway, oxidative stress, apoptosis, endothelial cell dysfunction

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