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HYPOXIA INDUCIBLE VEGF PRODUCTION IN SLEEP APNEA

睡眠呼吸暂停中缺氧诱导的 VEGF 产生

基本信息

批准号：
6644868
负责人：
ANDREW Peter LEVY
金额：
$ 12.5万
依托单位：
TECHNION-ISRAEL INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-30 至 2004-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6644868
关键词：
angiogenesis clinical research collateral circulation genetic polymorphism haptoglobins human subject hypoxia monocyte protein biosynthesis sleep apnea vascular endothelial growth factors

项目摘要

Angiogenesis is the physiological adaptive response of a tissue to hypoxia. The coronary collateral circulation of the heart represents such an adaptive response and is an important determinant in the extent of tissue damage following myocardial infarction. Autopsy studies have shown that only 50 percent of patients with coronary artery stenosis develop collaterals. A fundamental challenge in understanding the angiogenic response to ischemia in the clinical setting is to elucidate the basis for interindividual differences in the degree of collateral blood vessel formation. Recent evidence demonstrates the importance of differences between patients in the hypoxic regulation of the angiogenic growth factor, vascular endothelial growth factor (VEGF) in determining the extent of collateral blood vessel formation. Specifically, individuals who upregulate VEGF to a greater degree with hypoxia have more collateral blood vessels. The investigators intend to investigate the mechanism for this heterogeneity in the hypoxic regulation of VEGF. Accordingly, the specific aims of this project are: (1) Analysis of interindividual heterogeneity in hypoxia-inducible VEGF production in patients with obstructive sleep apnea syndrome (OSAS) in vivo and in vitro and its relationship to coronary collaterals; (2) Determination of the molecular mechanism for interindividual heterogeneity in VEGF production in response to hypoxia. These studies may lead to the development of new strategies to increase VEGF production in the setting of ischemic heart disease and thereby promote therapeutic angiogenesis. In addition, understanding the mechanism of interindividual heterogeneity in VEGF production in response to hypoxia would be of tremendous importance for understanding and predicting the natural history of a wide variety of diseases involving VEGF including tumor angiogenesis, diabetic retinopathy, rheumatoid arthritis, and inflammatory bowel disease.

血管生成是组织对缺氧的生理适应性反应。心脏的冠状动脉侧支循环代表了这样一种适应性是组织损伤程度的重要决定因素心肌梗死后。尸检研究表明， %的冠状动脉狭窄患者出现侧支循环。一了解缺血性心脏病血管生成反应的基本挑战临床背景是阐明个体间差异的基础，侧支血管形成的程度。最近的证据证明了患者之间在缺氧的重要性差异，调节血管生成生长因子、血管内皮生长因子血管内皮生长因子（VEGF）在确定侧支血管形成的程度。具体来说，缺氧时VEGF上调程度更高的个体有更多的侧支血管调查人员打算调查这种异质性的机制在缺氧调节VEGF。因此，本项目的具体目标是：（1）分析患者缺氧诱导VEGF产生的个体间异质性阻塞性睡眠呼吸暂停综合征（OSAS）的体内和体外研究，与冠状动脉侧支的关系;（2）分子水平的测定 VEGF产生的个体间异质性机制缺氧这些研究可能会导致制定新的战略，增加缺血性心脏病背景下VEGF的产生，促进治疗性血管生成。此外，了解缺氧反应中VEGF产生的个体间异质性，对于理解和预测自然界中多种涉及VEGF的疾病史，包括肿瘤血管生成、糖尿病视网膜病变、类风湿性关节炎和炎性肠道疾病。