Sydow Karsten, Münzel Thomas
Falk Cardiovascular Research Center, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Atheroscler Suppl. 2003 Dec;4(4):41-51. doi: 10.1016/s1567-5688(03)00033-3.
Elevated plasma concentrations of the endogenous nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) represent a novel risk factor for the development of endothelial dysfunction and a predictor for all-cause and cardiovascular mortality. However, it is unknown whether elevated ADMA plasma concentrations may be considered simply as a marker for cardiovascular disease or whether increased ADMA levels per se may predispose to the development of vascular disease. There is experimental and clinical evidence linking endothelial dysfunction to increased production of oxygen-derived free radicals such as superoxide anion. Oxidative stress has been shown to increase the activity of arginine methylating and ADMA degrading enzymes leading to increased ADMA concentrations. Interestingly, the endothelial nitric oxide synthase may become uncoupled in the presence of high ADMA levels further contributing to the vascular oxidative stress burden. It remains to be established to what extent ADMA is able to interact with eNOS in vivo. Possible mechanisms underlying increased oxidative stress in the setting of elevated ADMA concentrations and therapeutic implications will be discussed.
内源性一氧化氮合酶（eNOS）抑制剂非对称二甲基精氨酸（ADMA）的血浆浓度升高是内皮功能障碍发生的一种新的危险因素，也是全因死亡率和心血管死亡率的一个预测指标。然而，尚不清楚ADMA血浆浓度升高是否仅可被视为心血管疾病的一个标志物，或者ADMA水平升高本身是否可能易导致血管疾病的发生。有实验和临床证据将内皮功能障碍与超氧阴离子等氧衍生自由基的产生增加联系起来。氧化应激已被证明会增加精氨酸甲基化和ADMA降解酶的活性，导致ADMA浓度升高。有趣的是，在高ADMA水平存在的情况下，内皮一氧化氮合酶可能会解偶联，进一步加重血管氧化应激负担。ADMA在体内与eNOS相互作用的程度还有待确定。将讨论ADMA浓度升高情况下氧化应激增加的潜在机制及其治疗意义。
