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

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 HO 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 HO-induced AKT activation remains unclear.

MATERIAL AND METHODS

Human coronary artery endothelial cells (HCAECs) were used. The cells were treated with HO, 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 HO-induced oxidative stress and apoptosis in HCAECs. Co-treatment with captopril and the AKT inhibitor MK-2206 reduced the HO-induced P53 and ICAM-1 protein expression ( < 0.05). The proliferation, migration and invasion of HCAECs were significantly enhanced by co-treatment with captopril and MK-2206 ( < 0.05).

CONCLUSIONS

The study revealed the protective effect of captopril against HO-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.