HYPOXIA INDUCIBLE VEGF PRODUCTION IN SLEEP APNEA

血管生成是组织对低氧的生理适应性反应。 心脏的冠状侧支循环代表了这样一种适应性 反应，是组织损伤程度的重要决定因素 在心肌梗死后。尸检研究表明，只有50人 冠脉狭窄的患者中有1%会发生侧支循环。一个 了解脑缺血后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 论证了患者之间在低氧情况下区别对待的重要性 血管生成生长因子、血管内皮生长因子的调控 血管内皮生长因子(VEGF)在判断侧支血管形成程度中的作用。 具体地说，在缺氧的情况下，血管内皮生长因子的上调程度更高 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于对血管内皮生长因子的低氧调节。 因此，本项目的具体目标是：(1)分析 低氧诱导的血管内皮生长因子产生的个体间异质性 阻塞性睡眠呼吸暂停综合征(OSAS)的体内外研究 与冠脉的关系；(2)分子的测定 血管内皮生长因子产生的个体间异质性的机制 缺氧。这些研究可能会导致制定新的战略来 在缺血性心脏病的背景下增加血管内皮生长因子的产生 促进治疗性血管生成。此外，了解其作用机制 低氧反应中血管内皮生长因子产生的个体间异质性 对于理解和预测自然环境具有极其重要的意义 包括肿瘤在内的多种涉及血管内皮生长因子的疾病的病史 血管生成、糖尿病视网膜病变、类风湿性关节炎和炎症 肠病。

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.