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.The overall hypothesis of this proposal is that increased oxidative stress contributes to the pathogenesis of human heart failure. The purpose of this study is to test the hypothesis that systemic oxidative stress is increased in patients with systolic heart failure, and is associated with more rapid disease progression. In 100 patients with LV systolic dysfunction, we will measure 8-isoprostanes in the blood as a marker of systemic oxidative stress at baseline and annually for 3 years. We will correlate 9-isoprostanes with cardiac troponin I (cTnI), a measure of ongoing myocardial damage, and LV end-diastolic volume (LVEDV) by magnetic resonance imaging, a measure of structural remodeling. In addition, we will test the hypothesis that polymorphisms of manganese superoxide disumtase (MnSOD), the major SOD in the myocardium, lead to increased oxidative stress and more rapid disease progression in patients with heart failure. In patients studied in Aim 1 we will determine the presence of the -9Ala/Val polymorphism of MnSOD that has been associated with reduced enzyme activity. The presence of this polymorphism will be correlated to 8-isoprostanes and remodeling markers from Aim 1.
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