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Renin-angiotensin system inhibitor attenuates oxidative stress induced human coronary artery endothelial cell
Xuekun Shi1, Yuhua Guan2, Shaoyan Jiang1
1Department of Cardiovasology, the Affiliated Cardiovascular Hospital of Qindao University, Qindao, Shaodong, China.
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.
Insights
The renin-angiotensin system inhibitor captopril protects against oxidative stress and improves endothelial cell survival by modulating the AKT/mTOR pathway. This suggests captopril as a potential therapeutic for cardiovascular diseases.
Area of Science:
- Cardiovascular Science
- Endothelial Cell Biology
- Molecular Medicine
Background:
- The renin-angiotensin system (RAS) influences blood pressure, inflammation, oxidative stress, and insulin resistance.
- While RAS can decrease oxidative stress, its role in oxidative stress-induced endothelial dysfunction and H2O2-mediated AKT activation is unclear.
- Hydrogen peroxide (H2O2) stimulation increases oxidative stress and activates the AKT/mTOR pathway.
Purpose of the Study:
- To investigate the protective effects of the RAS inhibitor captopril against H2O2-induced endothelial cell dysfunction.
- To elucidate the role of the AKT/mTOR pathway in captopril's protective mechanisms.
- To evaluate captopril's impact on cell viability, proliferation, migration, and invasion.
Main Methods:
- Human coronary artery endothelial cells (HCAECs) were treated with H2O2, captopril, an AKT inhibitor (MK-2206), and an AKT activator (SC79).
- Western blot was used to measure p53, ICAM-1, p-eNOS, p-Akt, and mTOR.
- Cell viability, ROS levels, proliferation, migration, and invasion were assessed using MTT assay, flow cytometry, BrdU labeling, wound healing, and Transwell assays, respectively.
Main Results:
- Captopril reversed H2O2-induced oxidative stress and apoptosis in HCAECs.
- Combined treatment with captopril and MK-2206 reduced H2O2-induced p53 and ICAM-1 expression (p < 0.05).
- Captopril and MK-2206 co-treatment significantly enhanced HCAEC proliferation, migration, and invasion (p < 0.05).
Conclusions:
- Captopril demonstrates a protective effect against H2O2-induced endothelial cell dysfunction via the AKT/mTOR pathway.
- Captopril enhances endothelial cell survival, proliferation, migration, and invasion.
- These findings offer insights into captopril's therapeutic potential for cardiovascular diseases.
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