Guo Yan, Xing Liwan, Qian Chaodong, Ding Zhishan, Jin Bo
College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
Evid Based Complement Alternat Med. 2018 Jul 8;2018:8246560. doi: 10.1155/2018/8246560. eCollection 2018.
Atherosclerosis is the commonest cause of death in the world and one of the most important processes that occurs with increasing age because it is accompanied by progressive endothelial dysfunction. Recent studies demonstrated that Sirtuin 1 (SIRT1) might potentially affect cell senescence. However, the effect of SIRT1 on the regulation of human umbilical vein endothelial cell (HUVEC) senescence with total flavonoids (TFs) has not been addressed previously. This study investigated how SIRT1 functions in the process of HUVEC senescence when TFs are present and identified the potential molecular mechanisms involved. Using a model of HUVEC senescence induced by angiotensin II, TFs pretreatment reduced the percentage of senescence-associated -galactosidase (SA--gal) cells and p53 mRNA expression. The level of SIRT1 protein and E2F1 decreased during HUVEC senescence and could be partially recovered when cells were coincubated with TFs, while the levels of proteins p53 and p21 increased during cell senescence and diminished in response to the TFs treatment. When coincubated with 20 mM nicotinamide, the results with SA--gal-positive cells and the expression of SIRT1, E2F1, p53, and p21 were contrary to that obtained with only TFs pretreatment. The data indicate that the TFs exert their effect on HUVEC senescence through SIRT1.
动脉粥样硬化是全球最常见的死亡原因，也是随着年龄增长而出现的最重要的病理过程之一，因为它伴随着进行性内皮功能障碍。最近的研究表明，沉默信息调节因子1（SIRT1）可能潜在地影响细胞衰老。然而，SIRT1对总黄酮（TFs）调节人脐静脉内皮细胞（HUVEC）衰老的影响此前尚未见报道。本研究探讨了在存在TFs的情况下SIRT1在HUVEC衰老过程中的作用机制，并确定了其中潜在的分子机制。利用血管紧张素II诱导的HUVEC衰老模型，TFs预处理降低了衰老相关β半乳糖苷酶（SA-β-gal）阳性细胞的百分比以及p53 mRNA表达。在HUVEC衰老过程中，SIRT1蛋白和E2F1水平下降，而当细胞与TFs共同孵育时可部分恢复，而p53和p21蛋白水平在细胞衰老过程中升高，在TFs处理后降低。当与20 mM烟酰胺共同孵育时，SA-β-gal阳性细胞以及SIRT1、E2F1、p53和p21表达的结果与仅进行TFs预处理时相反。数据表明，TFs通过SIRT1对HUVEC衰老发挥作用。
