Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China; Vascular Biology Center, Department of Medicine, Medical College of Georgia/Georgia Regents University, 1459 Laney Walker Blvd, Augusta, GA 30912, USA.
Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
Biochem Biophys Res Commun. 2014 Apr 18;446(4):952-8. doi: 10.1016/j.bbrc.2014.03.035. Epub 2014 Mar 17.
Oxidative stress contributes to endothelial cell (EC) dysfunction, which is prevalent in ageing and atherosclerosis. MicroRNAs (miRs) are small, non-coding RNAs that post-transcriptionally regulate gene expression and play a key role in fine-tuning EC functional responses, including apoptosis and angiogenesis. MiR-92a is highly expressed in young endothelial cells in comparison with senescent endothelial cells, which exhibit increased oxidative stress and apoptosis. However, the impact of miR-92a treatment on EC viability and angiogenesis under oxidative stress is unknown. Hydrogen peroxide (H2O2) was used to induce oxidative stress in human umbilical vein endothelial cells (HUVEC). Pre-miR-92a treatment decreased H2O2-induced apoptosis of HUVEC as determined by TUNEL assay. Pre-miR-92a treatment enhanced capillary tube formation by HUVEC under oxidative stress, which was blocked by LY294002, an inhibitor of Akt phosphorylation. Interestingly, we also observed that inhibition of miR-92a by anti-miR-92a antisense can also enhance angiogenesis in HUVEC with and without oxidative stress exposure. Our results show that perturbation of miR-92a levels outside of its narrow "homeostatic" range may trigger endothelial cell angiogenesis, suggesting that the role of miR-92a in regulating angiogenesis is controversial and may vary depending on the experimental model and method of regulating miR-92a.
氧化应激导致内皮细胞 (EC) 功能障碍，这种情况在衰老和动脉粥样硬化中很常见。微小 RNA (miRs) 是小的非编码 RNA，可在后转录水平上调节基因表达，并在精细调节 EC 功能反应中发挥关键作用，包括细胞凋亡和血管生成。与衰老的内皮细胞相比，miR-92a 在年轻的内皮细胞中高度表达，衰老的内皮细胞表现出增加的氧化应激和细胞凋亡。然而，miR-92a 处理对氧化应激下 EC 活力和血管生成的影响尚不清楚。过氧化氢 (H2O2) 用于诱导人脐静脉内皮细胞 (HUVEC) 中的氧化应激。TUNEL 测定表明，前 miR-92a 处理可降低 H2O2 诱导的 HUVEC 细胞凋亡。前 miR-92a 处理增强了氧化应激下 HUVEC 的毛细血管管形成，该作用被 Akt 磷酸化抑制剂 LY294002 阻断。有趣的是，我们还观察到，抗 miR-92a 反义寡核苷酸抑制 miR-92a 也可以增强有或没有氧化应激暴露的 HUVEC 中的血管生成。我们的结果表明，miR-92a 水平的波动超出其狭窄的“内稳态”范围可能会触发内皮细胞血管生成，这表明 miR-92a 在调节血管生成中的作用存在争议，并且可能因实验模型和调节 miR-92a 的方法而异。
