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.Metabolic syndrome is a clustering of risk factors for heart disease. Blood vessels should dilate or contract in response to different stimuli, such as increased blood pressure, to prevent drastic changes in blood pressure. When the blood vessels do not function properly this is usually the result of endothelial dysfunction. Insulin is a hormone that converts blood sugar, or glucose, into useable energy. Insulin resistance occurs when the body no longer has the ability to produce or release the right amount of insulin. Endothelial dysfunction and insulin resistance are two key components of the metabolic syndrome. Increases in age, total and abdominal obesity, physical inactivity, cholesterol, and blood pressure are generally associated with endothelial dysfunction and insulin resistance. Importantly, we know that inflammation and oxidative stress are associated with endothelial function and insulin resistance. Oxidative stress is the exposure of the body's cells to molecules (i.e. reactive oxygen species) that are generated continuously in the body as a function of normal metabolism. Reactive oxygen species can produce damage to cells and interfere with the body's normal function, such as the ability of blood vessels to dilate or produce insulin. In humans we are unable to block oxidative stress, but we can block inflammation. Accordingly, the proposed research will test the hypothesis that inhibition of inflammation may improve endothelial dysfunction and insulin resistance in individuals varying in age, adiposity, habitual physical activity levels, plasma lipids and lipoproteins, and/or blood pressure, but without clinical cardiovascular or metabolic diseases. Furthermore, the proposed research will determine the molecular mechanisms involved in these processes.
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