Lung vascular responses--intermittent/sustained hypoxia

描述（由申请人提供）：睡眠呼吸暂停是一种复杂的疾病，其特征是间歇性缺氧（IH）反复发作，增加心血管疾病的风险。间歇性和持续性缺氧以各种不同的方式影响全身和肺血管系统。长期暴露于持续缺氧（SH）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被完全理解。为了更好地理解这些机制，我们将使用微阵列研究数千种基因对IH和SH的反应行为。我们将使用传统的细胞和分子方法来测试由微阵列数据产生的假设。我们假设系统和肺血管系统对间歇性（IH）和持续性缺氧（SH）的不同生理反应是由不同的基因表达模块调节的。在三个靶器官（肺、肺动脉和主动脉）中，研究间歇性和持续性缺氧时基因表达模式的详细时间变化将使我们能够识别这些基因组程序。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）中的基因表达模式；2)研究三种靶器官中SH应答的基因表达模式；3)确定决定IH和SH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.