Background
Vascular smooth muscle cells (VSMCs) senescence is a crucial factor relevant to accelerate cardiovascular diseases. Resveratrol (RES) has been reported that could obstruct vascular senescence. However, the detailed molecular mechanisms of RES in VSMCs senescence are still indistinct and deserve further investigations.
Conclusion
In conclusion, RES mitigated Ang II-induced VSMCs senescence by suppressing oxidative stress and mitochondrial dysfunction through activating E2F1/SOD2 axis. Our study disclosed that RES might be a potential drug and the axis of its regulatory mechanism might be therapeutic targets for postponing vascular senescence.
Results
In this study, VSMCs were treated with 100 nM angiotensin II (Ang II) for 3 days and then followed with a range of different concentrations of RES (0.5, 5, 15, 25, 35, 50 μM), and 25 μM of RES was chose for following experiments. We found that the E2F1 and SOD2 expressions were reduced in Ang II-induced VSMCs. RES treatment impeded Ang II-induced oxidative stress and mitochondrial dysfunction through elevating E2F1 and SOD2 expression, thereby alleviating VSMCs senescence. Additionally, E2F1 knockdown reversed the protective effects of RES on VSMCs senescence caused by Ang II administration. Ch-IP assay and dual luciferase reporter gene assay validated that E2F1 could bind to the promoter region of SOD2. Furthermore, E2F1 or SOD2 overexpression blocked Ang II-induced on VSMCs senescence.