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

• 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
• 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

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.

项目总结