REACTIVE OXYGEN SPECIES IN HUMAN HEART FAILURE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该建议的总体假设是，氧化应激增加有助于人类心力衰竭的发病机制。 本研究的目的是验证收缩性心力衰竭患者全身氧化应激增加，并与更快的疾病进展相关的假设。 在100例左心室收缩功能障碍患者中，我们将在基线和每年连续3年测量血液中的8-异前列腺素作为全身氧化应激的标志物。 我们将通过磁共振成像将9-异前列腺素与心肌肌钙蛋白I（cTnI）（持续心肌损伤的指标）和左室舒张末期容积（LVEDV）（结构重塑的指标）相关联。 此外，我们将测试的假设，锰超氧化物歧化酶（MnSOD），在心肌中的主要SOD的多态性，导致增加的氧化应激和更快的疾病进展的心力衰竭患者。 在目标1中研究的患者中，我们将确定与酶活性降低相关的MnSOD的-9 Ala/瓦尔多态性的存在。 该多态性的存在将与来自Aim 1的8-异前列烷和重塑标志物相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.