Lung vascular responses--intermittent/sustained hypoxia

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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.