eNOS Promoter Activation by Estrogen in Vascular Cells

血管细胞中雌激素对 eNOS 启动子的激活

• 批准号: 6837799
• 负责人: ULLA M HANSEN
• 金额: $ 5.65万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6837799
• 关键词: Adenoviridae; binding sites; cell line; chromatin immunoprecipitation; estrogen receptors; estrogens; genetic enhancer element; genetic promoter element; genetic regulation; genetic transcription; hormone regulation /control mechanism; nitric oxide synthase; protein isoforms; recombinant virus; transcription factor; transfection /expression vector; vascular endothelium

DESCRIPTION (provided by applicant): Understanding the molecular bases for the cardiovasculature protective effects of estrogen is essential in order ultimately to develop ligands for prevention and treatment of cardiovasculature disease in both men and women. Estrogen is protective against damage to the vasculature largely due to direct effects on vascular endothelial cells and smooth muscle cells. Both cell types express estrogen receptors (ERs), the physiological targets of estrogen. Nuclear ERs are hormone-activated, DNA-binding transcription factors. Vascular endothelial cells respond to estrogen both in a rapid "nongenomic" manner and in a longer-term manner, which involves transcriptional regulation of estrogen receptor-target genes. A critical target for estrogen protection of the vasculature is endothelial nitric oxide synthase (eNOS), whose promoter is activated by ligand. The long-term goal of this proposal is to elucidate the molecular mechanism by which ER induces eNOS gene expression. The specific aims include: 1) identifying which ER - ERalpha and/or ERbeta - activates the eNOS promoter, and 2) specifying the promoter elements that promote association with ER, and probing whether endothelial-specific transcription factors are involved in the estrogen response.

描述（由申请人提供）：为了最终开发用于预防和治疗男性和女性心血管疾病的配体，了解雌激素的心血管保护作用的分子基础是必不可少的。雌激素主要由于对血管内皮细胞和平滑肌细胞的直接作用而对血管系统的损伤具有保护作用。两种细胞类型都表达雌激素受体（ER），雌激素的生理靶点。细胞核ER是一种转录激活的DNA结合转录因子。 血管内皮细胞对雌激素的反应既有快速的“非基因组”方式，也有较长期的方式，这涉及雌激素受体靶基因的转录调控。雌激素保护血管系统的关键靶点是内皮型一氧化氮合酶（eNOS），其启动子被配体激活。本研究的长期目标是阐明ER诱导eNOS基因表达的分子机制。具体目标包括：1）鉴定哪一种ER-ER α和/或ER β激活eNOS启动子，和2）确定促进与ER结合的启动子元件，并探测内皮特异性转录因子是否参与雌激素应答。