Liu Lei, Yang Xiuhua, Liao Yiyang, Wang Chuanhua, Wang Yuanliang
College of Food Science and Technology, Hunan Agricultural University, Changsha, Hunan 410125, China.
Hunan Economic & Trade Senior Technical School, Xiangtan, Hunan 410004, China.
Toxicol Res (Camb). 2022 Sep 3;11(5):831-840. doi: 10.1093/toxres/tfac051. eCollection 2022 Oct.
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.
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.
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.
血管平滑肌细胞（VSMCs）衰老 是加速心血管疾病的一个关键因素。据报道，白藜芦醇（RES）可阻止血管衰老。然而，RES在VSMCs衰老中的详细分子机制仍不清楚，值得进一步研究。
在本研究中，VSMCs用100 nM血管紧张素II（Ang II）处理3天，然后用一系列不同浓度的RES（0.5、5、15、25、35、50 μM）处理，后续实验选择25 μM的RES。我们发现，在Ang II诱导的VSMCs中，E2F1和SOD2表达降低。RES处理通过提高E2F1和SOD2表达，抑制了Ang II诱导的氧化应激和线粒体功能障碍，从而减轻了VSMCs衰老。此外，E2F1基因敲低逆转了RES对Ang II诱导的VSMCs衰老的保护作用。Ch-IP实验和双荧光素酶报告基因实验验证了E2F1可以结合到SOD2的启动子区域。此外，E2F1或SOD2过表达可阻断Ang II诱导的VSMCs衰老。
总之，RES通过激活E2F1/SOD2轴抑制氧化应激和线粒体功能障碍，减轻了Ang II诱导的VSMCs衰老。我们的研究表明，RES可能是一种潜在药物，其调控机制轴可能是延缓血管衰老的治疗靶点。
