The role of ADMA in the pathology of asthma

ADMA 在哮喘病理学中的作用

• 批准号: 7271957
• 负责人: SANDRA M WELLS
• 金额: $ 2.89万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7271957
• 关键词: Amino Acids; Animal Model; Arginine; Asthma; Biological Availability; Blood Circulation; Blood Vessels; Cardiovascular Diseases; Cell Proliferation; Cells; Characteristics; Chronic; Clinical; Collagen; Condition; Data; Development; Disease; Elevation; Endothelial Cells; Enzyme Uncoupling; Enzymes; Epithelial Cells; Exhalation; Extrinsic asthma; Fellowship; Functional disorder; Generations; Goals; Homeostasis; Individual; Infiltration; Inflammation; Inflammatory; Interphase Cell; Laboratories; Lead; Link; Liquid substance; Measures; Mediator of activation protein; Modeling; Mus; N,N-dimethylarginine; Names; Nitric Oxide; Nitric Oxide Synthase; Numbers; Ornithine; Ovalbumin; Oxidative Stress; Pathogenesis; Pathology; Patients; Peroxonitrite; Plasma; Play; Polyamines; Production; Proline; Publishing; Range; Reaction; Regulation; Relative (related person); Reporting; Rest; Role; Serum; Severities; Superoxides; Testing; Urea; Vasodilator Agents; airway hyperresponsiveness; airway inflammation; airway remodeling; antigen challenge; arginase; asthmatic patient; base; cardiovascular risk factor; expectation; in vivo; inhibitor/antagonist; insight; macrophage; novel

DESCRIPTION (provided by applicant): Inflammation plays a central role in the pathogenesis of asthma. One important inflammatory mediator is nitric oxide (NO), a vasodilator of the bronchial circulation. Recent studies suggest that asthma may be a condition of decreased NO bioavailability. NO is produced by L-arginine (L-arg) by NO syntheses (NOS). It has been recently reported that a decreased L-arg bioavailability in asthmatic patients likely contributes to the NO deficiency in asthma. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS, has been established as a novel cardiovascular risk factor and its accumulation has been reported in a variety of disorders. Although clinical and experimental evidence indicates that elevation of ADMA may cause a relative L-arg deficiency, no data are available on the relative ADMA levels in asthmatic patients. Therefore, the goal of this proposal is to determine the mechanism of ADMA's effects in epithelial cells and demonstrate an in vivo association between ADMA levels and the pathology of asthma using a murine model. Upon successful completion of this proposal, our expectation is that these studies will not only provide new insights into the pathology of asthma, but also potentially identify a novel factor in the development of this disease.

描述（由申请人提供）：炎症在哮喘的发病机制中起着核心作用。一种重要的炎症介质是一氧化氮 (NO)，它是支气管循环的血管扩张剂。最近的研究表明，哮喘可能是一氧化氮生物利用度降低的一种病症。 NO 由 L-精氨酸 (L-arg) 通过 NO 合成 (NOS) 产生。最近有报道称，哮喘患者 L-arg 生物利用度降低可能导致哮喘中 NO 缺乏。不对称二甲基精氨酸 (ADMA) 是一种 NOS 内源性抑制剂，已被确定为一种新型心血管危险因素，并且已报道其在多种疾病中蓄积。尽管临床和实验证据表明 ADMA 升高可能导致相对 L-arg 缺乏，但没有关于哮喘患者相对 ADMA 水平的数据。因此，本提案的目标是确定 ADMA 对上皮细胞的作用机制，并使用小鼠模型证明 ADMA 水平与哮喘病理之间的体内关联。该提案成功完成后，我们期望这些研究不仅将为哮喘病理学提供新的见解，而且有可能确定这种疾病发展的新因素。