The role of ADMA in the pathology of asthma

ADMA 在哮喘病理学中的作用

基本信息

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
项目类别：
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

项目摘要

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理中起着核心作用。一个重要的炎症介质是一氧化氮（NO），这是支气管循环的血管扩张剂。最近的研究表明，哮喘可能是没有生物利用度降低的条件。 L-精氨酸（L-ARG）由NO合成（NOS）产生。据报道，哮喘患者的L-Arg生物利用度降低可能导致哮喘无缺乏症状。非对称二甲基精氨酸（ADMA）是一种NOS的内源性抑制剂，已成为一种新型的心血管危险因素，并且已经报道了多种疾病的积累。尽管临床和实验证据表明，ADMA的升高可能导致相对L-ARG缺乏症，但哮喘患者的相对ADMA水平没有可用的数据。因此，该提案的目的是确定ADMA在上皮细胞中的作用机理，并使用鼠模型证明ADMA水平与哮喘病理之间的体内关联。成功完成该提案后，我们的期望是，这些研究不仅将为哮喘的病理提供新的见解，而且还可以确定这种疾病发展的新因素。