REACTIVE OXYGEN SPECIES IN HUMAN HEART FAILURE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这一建议的总体假设是，氧化应激增加有助于人类心力衰竭的发病机制。 这项研究的目的是检验这一假设，即收缩性心力衰竭患者的全身氧化应激增加，并与更快的疾病进展有关。在100名左心室收缩功能不全的患者中，我们将在基线和3年内每年检测血液中的8-异前列腺素作为全身氧化应激的标志。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)和左室舒张末期容量(LVEDV)相关联，心肌肌钙蛋白I(CTnI)是正在进行的心肌损伤的衡量指标，左室舒张末期容量(LVEDV)是结构重构的衡量标准。 此外，我们还将验证这样一种假设，即心肌中主要的超氧化物歧化酶--锰超氧化物歧化酶(MnSOD)的多态性会导致心力衰竭患者氧化应激增加，疾病进展更快。在目标1中研究的患者中，我们将确定是否存在与酶活性降低相关的MnSOD-9Ala/Val多态。这种多态的存在将与来自AIM 1的8-异前列腺素和重塑标记物相关。

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.