A microRNA-target Network in Endothelial DNA Damage and Angiogenesis

项目摘要 内皮细胞在调节心血管健康的几个方面发挥重要作用。我们的实验室 确定了一组7种在DNA损伤和氧化应激过程中上调的microRNA（miRs）， 内皮细胞这些miR中的一些诱导内皮细胞中的DNA损伤、细胞死亡和衰老。 体外和体内。我们已经将DNA损伤网络表征为这些miR的靶点。这项建议 目的是调查A）这些miR是如何在应对压力时受到调节的？B）有哪些机制 通过这些miR-靶标网络相互作用导致内皮死亡和功能障碍，最后C） 通过靶向该miR-靶点网络和与以下药物的任何潜在协同作用来评估新的抗血管生成策略： 体内VEGF抑制。我们的研究将建立一个新的模式，抑制血管生成使用miR- 介导的DNA修复中断。

Project Summary Endothelial cells play an important role in regulating several aspects of cardiovascular health. Our lab has identified a group of seven microRNAs (miRs) that are upregulated during DNA damage and oxidative stress in endothelial cells. Some of these miRs induce DNA damage, cell death and senescence in endothelial cells in vitro and in vivo. We have characterized a DNA damage network as being targets of these miRs. This proposal aims to investigate A) How these miRs are regulated in response to stressors? B) What are the mechanisms by which these miR-target network interactions lead to endothelial death and dysfunction and finally C) evaluate a novel anti-angiogenic strategy by targeting this miR-target network and any potential synergy with VEGF inhibition in vivo. Our studies will establish a new paradigm for inhibiting angiogenesis using miR- mediated disruption of DNA repair.