Asymmetric Dimethylarginine (ADMA), Genetic Variation, and Cardiovascular Disease

不对称二甲基精氨酸 (ADMA)、遗传变异和心血管疾病

• 批准号: 7760733
• 负责人: Jennifer K Pai
• 金额: $ 25.04万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7760733
• 关键词: Age; Alcohol consumption; Alcohols; Archives; Arginine; Atherosclerosis; Biochemical; Biological; Blood specimen; Body mass index; Cardiovascular Diseases; Cardiovascular system; Cohort Studies; Congestive Heart Failure; Coronary heart disease; Data; Diabetes Mellitus; Dietary Factors; Disease; Dyslipidemias; Enzymes; Event; Functional disorder; Future; Genes; Genetic Polymorphism; Genetic Variation; Goals; Health; Health Professional; Hip region structure; Hypertension; Inflammatory; Insulin Resistance; Interleukin-6; Lead; Life Style; Link; Lipids; Maps; Measures; Metabolism; Myocardial Infarction; N,N-dimethylarginine; Nested Case-Control Study; Nitric Oxide Synthase; Nurses; Oxidative Stress; Pathway interactions; Peripheral arterial disease; Plasma; Predictive Value; Prevention; Process; Proteins; Questionnaires; Risk; Risk Factors; Smoking; Specimen; Stress; Stroke; Tissues; Tumor Necrosis Factor Receptor; Variant; Woman; atherogenesis; cardiovascular disorder risk; cardiovascular risk factor; dimethylarginine; follow-up; improved; inflammatory marker; inhibitor/antagonist; innovation; insulin sensitivity; lifestyle factors; men; novel; novel therapeutic intervention; premature; prevent; prospective

Growing evidence suggests that pathways in addition to innaraination and dyslipidemia contribute tothe undtsrlyiiig processes of atherosclen3sis;endathelial dysfunction, a Howcvcr,:,fGw studies liave examined tlielhterreiatioiis between oxidative istressj.endiottielial dysfui!(:l;ian,:and; CHD. Asymmetric dimethylarginlne (ADMA) Is an endogenous inliibitor of nitricoxidesynthase (NOS), anti has recently emerged p a potential novel risk mpt^ker iiietabolizedljy the enzyme, dimethylarginine diraethylaminohydrolase (DDAiHI), and increa stress inhibit DDAH activity in the tissues, which leads to sustained levels of ADMA. Accumulatipri ofADMA and reduced NO synthesis leads coendothellalciysfunction and also initiates and promoteiu processes involved with atherogenesis. Plasrha ADMA levels have been associated with several risk factors oif GHD; however, data on the predictive valite of ADMA, genetic variation iii the DDAH giene, arid the prospective risk of CHD in men and women have th its far been limited; The goal of this proposal is to irtvestigate plasma ADMA: levels as a novel biochemical predictor of CilD among tyvo large prospective cohort studies: the NufsCLs' Health Study (NHS) and the Health Professionals Foliow-up Study (HPFS). Both studies have over 22 years of repeated dietary and lifestyle questionnaire data, blood samples collected from 32,826'wonVen in NHf and,l,:8,225:men in HPFS, and nested case-control studies with biologiical specimens previously archived among Incident cases of nonfaial mypcardialinfari:tion or fatal CHD, and/age and smoking thatched conti"ols. The specific aims of this prpposal are to;!;) exaniihe^the'prospective relationship between plasma ADM control settings among men and womeri; 2.):UtiIlze the existing prospective data toexamine inteiTelations betvveen lifestylts^tlietai-y, arid other hiealth faCtoi-s,;and plasma ADMA to elueidale potential; mechanistris; and 3.) examine the.genetic variation in the DDAH gene with plasma ADMA levels and risk bf.GHD in both men and women. These findings may lead to new therapeutic interventions vvhich inhibltthe effects of ADMA arid prevent che progression df atherosclerosis and cardiovascular disease.

越来越多的证据表明，除了先天性和血脂异常之外，还有其他途径导致 动脉粥样硬化的 undtsrlyiiig 过程；内皮功能障碍， 如何cvcr,:,fGw 研究检查了氧化应激与内膜功能障碍之间的相互关系！(:l;ian,:and; 冠心病。不对称二甲基精氨酸 (ADMA) 是一氧化氮合成酶 (NOS) 的内源性抑制剂，具有抗氧化作用 最近出现了一个潜在的新风险 mpt^ker 代谢二甲基精氨酸二乙氨基水解酶 (DDAiHI)，并增加 压力会抑制组织中的 DDAH 活性，从而导致 ADMA 水平持续升高。 ADMA 的累积和 NO 合成减少导致共内皮细胞功能，并且还启动和促进涉及的过程 动脉粥样硬化。 Plasrha ADMA 水平与 GHD 的多种危险因素有关；然而，有关数据 ADMA 的预测价值、遗传变异 iii、DDAH giene、以及男性和女性患 CHD 的预期风险 妇女的地位至今仍受到限制；本提案的目标是研究血浆 ADMA：水平作为一种新的方法 tyvo 大型前瞻性队列研究中 CilD 的生化预测因子：NufsCLs 健康研究 (NHS) 和 卫生专业人员跟踪研究 (HPFS)。这两项研究都有超过 22 年的重复饮食和 生活方式问卷数据、从 NHf 中的 32,826 名 wonVen 和 HPFS 中的 8,225 名男性采集的血液样本，以及 使用先前在非失败事件案例中存档的生物标本进行巢式病例对照研究 心肌梗塞或致命性冠心病，和/年龄和吸烟茅草控制。本计划的具体目标是 to;!;) exaniihe^'血浆 ADM 之间的前瞻性关系 控制男性和女性的设置； 2.):利用现有的前瞻性数据来检查内部情况 不同的生活方式、以及其他健康因素；以及血浆 ADMA 来阐明潜力；机械师；和 3。） 检查 DDAH 基因的遗传变异与血浆 ADMA 水平和男性和女性 bf.GHD 的风险 女性。这些发现可能会导致新的治疗干预措施，从而抑制 ADMA 的作用并预防 动脉粥样硬化和心血管疾病的进展。