This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Obstructive sleep apnea (OSA) has been associated with increased cardiovascular morbidity and mortality by large epidemiological studies. Patients with OSA have higher incidence of vascular events such as stroke, myocardial infarction and hypertension. This effect seems to be dose related, meaning that the more severe OSA, the worse the outcome. At the present moment, the pathophysiological mechanisms leading to such cardiovascular outcomes have not been clearly identified. Patients with sleep apnea have recurrent periods of significant oxygen desaturation linked to each respiratory event. The recurrent desaturation leads to intermittent hypoxemia during sleep, which might be an important factor in the development of endothelial injury and endovascular thrombosis. One of the postulated mechanisms of endothelial injury is the activation of ATPDase on the endothelial surface, leading to increased platelet aggregation and microvascular thrombus formation. Another plausible mechanism is the shedding of endothelial cells into the circulation. This proposed research aims to evaluate both ATPDase activity in lymphocytes and circulating levels of endothelial cells in patients with nocturnal intermittent hypoxemia (NIH) and OSA and healthy controls. The mechanisms underlying the high incidence of vascular events in subjects with OSA will be evaluated. The evaluation of such mechanisms will lead to a better understanding of the pathways involved and the development of therapeutic strategies targeting the reduction or avoidance of endothelial injury with the ultimate goal to reduce the morbidity and mortality associated with such events.
The specific aims are to determine 1) the relationship between NIH and endothelial tissue damage by measuring the circulating endothelial cells (CEC) and 2) the relationship between NIH and endothelial cell dysfunction by quantifying ATPDase activity. As a secondary aim, this study proposes to evaluate the effect of sleep apnea treatment, which will suppress nocturnal intermittent hypoxemia, on the circulating levels of endothelial cells and on the ATPDase activity. The study hypothesizes that due to OSA leads to endothelial injury by increasing the activity of ATPDase and shedding of endothelial cells to the microcirculation. The related secondary hypothesis is that treatment of OSA decreases ATPDase activity and CEC levels due to obliteration of intermittent hypoxemia during sleep. If these hypotheses are shown to be correct, they will provide a mechanism illustrating how OSA increases the likelihood of the development of cardiovascular events, including hypertension, myocardial infarction and stroke.
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