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.Aging is a major risk factor for heart disease. Blood vessels should dilate or constrict in response to different stimuli, such as increased blood flow, to prevent drastic changes in blood pressure. When the blood vessels do not function properly this is usually the result of endothelial dysfunction. Increases in oxidative stress and inflammation are seen in aging and endothelial dysfunction. One way to lessen the age-related dysfunction is to exercise regularly. This study is looking at the role of peroxisome proliferator activated receptor alpha (PPARa) in dysfunction resulting from aging and physical inactivity. PPARa is a receptor in cells that affects expression of genes involved in oxidative stress and inflammation. We will increase PPARa activity with the drug fenofibrate. We expect that in older adults this increase in PPARa will improve endothelial function. The improvements in endothelial function will be related to reduced oxidative stress and inflammation. We also expect people who exercise regularly will have increased PPARa activity at baseline, and therefore their function will not be increased with fenofibrate.
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