Superoxide and Vascular Function in Heart Failure

心力衰竭中的超氧化物和血管功能

• 批准号: 7156539
• 负责人: Jordan D Miller
• 金额: $ 4.67万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-07 至 2008-08-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156539
• 关键词: antioxidants; cardiovascular function; cytoprotection; echocardiography; genetically modified animals; heart failure; heart surgery; isozymes; laboratory mouse; molecular pathology; nitric oxide; oxidative stress; polymerase chain reaction; postdoctoral investigator; protein structure function; superoxide dismutase; superoxides; vascular endothelium

DESCRIPTION (provided by applicant): Heart failure (HF) is an enormously important clinical problem. Impairment of endothelial function is associated with HF, and may contribute to the progression of HF by increasing ventricular afterload. As oxidative stress is a important determinant of endothelial function, these studies aim to: 1) determine the role of extracellular superoxide dismutase (ecSOD), an important antioxidant, in protection of endothelial function in HF, and 2) determine the role of the intracellular copper-zinc SOD (CuZnSOD) in the protection of endothelial function in HF. For Aim 1, aortic rings from mice deficient in ecSOD will be studied ex vivo to determine the contribution of endogenous ecSOD to preservation of endothelial function in HF. Mice overexpressing human ecSOD will also be studied ex vivo to determine if increases in ecSOD can protect endothelial function in HF. In Aim 2, aortic rings from mice deficient in CuZnSOD, as well as rings from transgenic mice overexpressing CuZnSOD will be studied ex vivo to determine the role of intracellular superoxide scavenging in HF. Collectively, these studies will lend important insights into the role of oxidative stress and vascular function in HF.

描述（由申请人提供）：心力衰竭（HF）是一个非常重要的临床问题。内皮功能的损害与HF有关，并且可能通过增加心室后负荷而导致HF的进展。由于氧化应激是内皮功能的重要决定因素，因此这些研究的目的是：1）确定细胞外超氧化物歧化酶（ECSOD）（一种重要的抗氧化剂）在保护HF中的内皮功能中的作用，而2）确定细胞内铜（Endssod）的作用。对于AIM 1，将研究来自ECSOD缺乏小鼠的主动脉环，以确定内源性ECSOD对保存HF内皮功能的贡献。还将对过表达人ECSOD的小鼠进行离体研究，以确定ECSOD的增加是否可以保护HF中的内皮功能。在AIM 2中，将研究来自Cuznsod缺乏的小鼠的主动脉环，以及过表达Cuznsod的转基因小鼠的环，以确定在HF中清除细胞内超氧化物的作用。总的来说，这些研究将为HF中氧化应激和血管功能的作用提供重要的见解。