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

越来越多的证据表明，除了内毒症和血脂异常外，还有其他途径也会导致 动脉粥样硬化的不稳定过程；内皮功能障碍 然而，FGW研究检查了氧化性内皮功能障碍之间的关系！(：L；伊恩，：和； 先心病。不对称二甲基精氨酸(ADMA)是一氧化氮合酶(NOS)的内源性抑制物，抗HAS 最近出现了一种潜在的新风险mpt^ker 降解二甲基精氨酸二乙氨基水解酶(DDAiHI)，并提高 应激抑制组织中的DDAH活性，从而导致ADMA的持续水平。ADMA和ADMA的累积率 NO合成减少导致血管内皮细胞功能，并启动和促进参与 动脉粥样硬化的形成。血浆ADMA水平与GHD的几个风险因素有关；然而，关于 ADMA的预测价值，DDAH基因变异III，以及男性和 女性的研究一直很有限；这项建议的目的是将血浆ADMA：水平作为一项新的研究 TYVO大型前瞻性队列研究中CILD的生化预测因素：NufsCLS健康研究(NHS)和 卫生专业人员逐级研究(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，血液样本从32,826‘WonVen在NHF和L，：8,225：男性在HPFS，和 先前在非儿童发病病例中存档的生物学标本的嵌套式病例对照研究 心肌梗塞：死亡或致命的冠心病，以及/年龄和吸烟。这篇文章的具体目的是 到；！；)Exaniihe^血浆ADM之间的预期关系 男性和女性之间的控制设置；2.)：利用现有的前瞻性数据来检查干扰 生活方式与其他健康因素之间的关系--S；血浆ADMA对潜势的影响；机制； 检测DDAH基因的遗传变异与血浆ADMA水平和Bf.GHD的风险 女人。这些发现可能导致新的治疗干预措施，即抑制ADMA的作用和预防 ChE进展与动脉粥样硬化和心血管疾病。

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.