NADPH Oxidase in Angiotensin II-induced Cardiac Fibrosis

NADPH 氧化酶在血管紧张素 II 诱导的心脏纤维化中的作用

• 批准号: 6835284
• 负责人: JOOYOUNG J SHIN
• 金额: $ 5.25万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6835284
• 关键词: NAD(P)H dehydrogenase; angiotensin II; cell differentiation; cell type; coronary disorder; electron spin resonance spectroscopy; enzyme activity; fibroblasts; fibrosis; fluorescent dye /probe; free radical oxygen; human tissue; laboratory mouse; phosphorylation; polymerase chain reaction; postdoctoral investigator; tissue /cell culture; ventricular hypertrophy; western blottings

DESCRIPTION (provided by applicant): This proposal investigates the roles of reactive oxgyen species and NAD(P)H oxidases in cardiac fibrosis induced by angiotensin II. NAD(P)H oxidases are the major sources of reactive oxygen species in cardiovascular cells. Previous work in this laboratory has shown that angiotensin II stimulates in vitro the production of reactive oxygen species and upregulates NAD(P)H expression in the pathophysiology of cardiac fibrosis. The transformation of fibroblasts to myofibroblasts represents a key process in cardiac fibrosis. This proposal addresses the following specific aims: 1) Determine whether an NAD(P)H oxidase mediates the transformation of fibroblasts into myofibroblasts by angiotensin II in vitro, and 2) Establish the role of NAD(P)H oxidases in mouse models of cardiac hypertrophy and fibrosis produced by chronic infusion of angiotensin II. Elucidation of the mechanisms by which cardiac fibroblasts transform into myofibroblasts during cardiac fibrosis will provide insight into the pathophysiology of human hypertensive heart disease and enable future development of specific inhibitors of adverse myocardial remodeling.

描述（由申请方提供）：本提案研究了活性氧物质和NAD（P）H氧化酶在血管紧张素II诱导的心脏纤维化中的作用。NAD（P）H氧化酶是心血管细胞中活性氧的主要来源。本实验室先前的工作已经表明，血管紧张素II在体外刺激活性氧的产生，并在心脏纤维化的病理生理学中上调NAD（P）H的表达。成纤维细胞向肌成纤维细胞的转化代表了心脏纤维化的关键过程。该提案提出了以下具体目标：1）确定NAD（P）H氧化酶是否在体外介导血管紧张素II将成纤维细胞转化为肌成纤维细胞，以及2）确定NAD（P）H氧化酶在慢性输注血管紧张素II产生的心脏肥大和纤维化小鼠模型中的作用。阐明心脏纤维化过程中心脏成纤维细胞转化为肌成纤维细胞的机制将为人类高血压心脏病的病理生理学提供深入了解，并使未来能够开发不良心肌重塑的特异性抑制剂。