Fat Biology, Sleep Disorders, and Cardiovascular Disease

Endothelial dysfunction, or abnormal functioning of the lining of blood vessels, appears to be a key process in the development of cardiovascular disease. Endothelial dysfunction appears to be caused by both sleep disordered breathing and obesity. As endothelial dysfunction is among the first clinical marker that predicts future cardiovascular events, understanding molecular mechanisms leading to impairment of endothelial function is very important. Endothelial function requires the proper functioning of endothelial nitric oxide synthase (eNOS). eNOS activity is tightly regulated by caveolin-1, a protein important in the formation of cellular structures called caveolae. Low levels of caveolin-1 facilitate optimal nitric oxide synthesis in endothelial cells as caveolin-1 helps to spatially organize eNOS in close proximity to signaling proteins that are important for eNOS activation. In certain diseases however, the balance of caveolin-1 and eNOS can be disrupted resulting in impaired nitric oxide synthesis and leading to endothelial dysfunction.

The investigators therefore seek to characterize levels of caveolin-1, and correlate this with the presence or absence of sleep disordered breathing, obesity, and cardiovascular disease. The current IRB protocol covers the performance of fat biopsies on subjects who have recently completed a sleep study either in the Center for Sleep Medicine or in our sleep laboratory and were found to have sleep disordered breathing or no sleep disordered breathing, subject with sleep disordered breathing who have been treated successfully with continuous positive airway pressure for 3-6 months, and subjects undergoing other studies in our lab who are obese or non-obese and subjects who have known cardiovascular disease and subjects without known cardiovascular disease.