A microRNA-target Network in Endothelial DNA Damage and Angiogenesis

内皮 DNA 损伤和血管生成中的 microRNA 靶网络

基本信息

批准号：
10202700
负责人：
Sudarshan Anand
金额：
$ 38.23万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10202700
关键词：
Affect Aging Ataxia Autoimmune Diseases Automobile Driving Binding Sites Biological Assay Blood Vessels CHEK2 gene Cardiovascular Diseases Cardiovascular system Cell Aging Cell Death Cell Line Cell Survival Cells Cellular Stress Cessation of life Complex DNA Damage DNA Double Strand Break DNA Repair Data Development Disease Double Strand Break Repair Endothelial Cells Endothelium FGF2 gene Functional disorder Genes Genetic Transcription Growth H2AFX gene Human In Vitro Injury KDR gene Lead Luciferases Macular degeneration Malignant Neoplasms Mediating MicroRNAs Modeling Mus Mutate Organ Oxidation-Reduction Oxidative Stress Pathogenesis Pathologic Neovascularization Pathology Pathway interactions Phenotype Phosphorylation Phosphotransferases Play Proliferating Proteins RNA-Directed DNA Polymerase Reagent Regulation Resistance Role Signal Transduction Small Interfering RNA Small RNA Stress TP53 gene Telomerase Telomere Maintenance Testing Tumor Angiogenesis Vascular Endothelial Growth Factors Vascular Endothelium Vegf inhibition Work angiogenesis biological adaptation to stress cardiovascular health endothelial dysfunction experimental study in vivo inhibitor/antagonist loss of function mutant novel novel therapeutics nuclease ocular angiogenesis promoter repair function response senescence sensor small molecule inhibitor stressor synergism targeted treatment therapeutic angiogenesis tool

项目摘要

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.

项目摘要内皮细胞在调节心血管健康的几个方面起着重要作用。我们的实验室有确定了一组七个microRNA（miR），这些microRNA（miR）在DNA损伤和氧化应激期间上调内皮细胞。其中一些miR诱导内皮细胞中的DNA损伤，细胞死亡和衰老体内和体内。我们将DNA损伤网络表征为这些miR的靶标。这个建议目的是研究a）如何根据压力源来调节这些miR？ b）有什么机制这些miR-target网络相互作用导致内皮死亡和功能障碍，最后C）通过针对这个miR-target网络以及与 VEGF抑制体内。我们的研究将建立一个新的范式，用于使用miR-抑制血管生成介导的DNA修复破坏。