Lung vascular responses--intermittent/sustained hypoxia

描述(申请人提供)：睡眠呼吸暂停是一种复杂的情况，其特征是反复发作间歇性低氧(IH)，增加心血管疾病的风险。间歇性和持续性低氧以不同和不同的方式影响全身和肺血管。长期暴露在持续低氧(SH)中会导致肺血管收缩和全身血管扩张。这些不同反应背后的分子程序还没有完全被理解。为了更好地理解这些机制，我们将使用微阵列来研究数千个基因对IH和SH的响应行为。我们将使用传统的细胞和分子方法来检验由微阵列数据产生的假设。我们假设，体循环和肺血管系统对间歇性低氧(IH)和持续性低氧(SH)的不同生理反应是由不同的基因表达模块调控的。研究间歇性和持续性低氧对三个靶器官(肺、肺动脉和主动脉)响应的基因表达模式随时间的详细变化将使我们能够识别这些基因组计划。我们的具体目标是：1)研究IH在三个靶器官(肺、肺动脉和主动脉)中的表达模式；2)研究SH在相同的三个靶器官中的表达模式；3)确定决定IH和SH之间差异反应的基因模块和网络。

DESCRIPTION (provided by applicant): Sleep apnea is a complex condition that is characterized by repeated episodes of intermittent hypoxia (IH) that increase the risk of cardiovascular morbidity. Intermittent and sustained hypoxia affect systemic and pulmonary vasculature in various and contrasting ways. Prolonged exposure to sustained hypoxia (SH) results in pulmonary vasoconstriction and systemic vasodilatation. The molecular programs underlying these disparate responses are not fully understood. To better understand these mechanisms, we will study the behavior of thousands of genes in response to IH and SH using microarrays. We will use traditional cell and molecular methods to test hypotheses generated by microarray data. We hypothesize that the differential physiological responses to intermittent (IH) and sustained hypoxia (SH) in systemic and pulmonary vascular systems are regulated by distinct gene expression modules. Studying the detailed time-coursed changes in gene expression patterns in response to intermittent and sustained hypoxia in three target organs (lung, pulmonary artery, and aorta) will allow us to identify these genomic programs. Our specific aims are: 1) To study gene expression patterns in response to IH in the three target organs (lung, pulmonary artery, and aorta); 2) To study gene expression patterns in response to SH in the same three target organs; and 3) To identify the gene modules and networks that determine the differential responses between IH and SH.