Asymmetric dimethyarginine as marker and mediator in ischemic stroke.
Asymmetric dimethyarginine as marker and mediator in ischemic stroke.
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DOI：
10.3390/ijms131215983
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发表时间：
2012-11-28
影响因子：
5.6
通讯作者：
Worthmann H
中科院分区：
文献类型：
--
作者：
Chen S;Li N;Deb-Chatterji M;Dong Q;Kielstein JT;Weissenborn K;Worthmann H
不对称二甲基精氨酸（ADMA）是一种内源性一氧化氮合酶（NOS）抑制剂，被认为是内皮细胞功能障碍和动脉粥样硬化的介质。循环ADMA水平与心血管危险因素相关，如高胆固醇血症、动脉高血压、糖尿病、高同型半胱氨酸血症、年龄和吸烟。因此，临床研究发现证据表明，ADMA水平升高与脑血管事件风险升高相关。急性缺血性卒中后，ADMA及其类似物对称二甲基精氨酸（SDMA）的水平通过蛋白质甲基化和氧化应激的增强而升高。此外，通过二甲基精氨酸二甲基氨基水解酶（DDAH）的ADMA裂解减少。这种二甲基精氨酸的增加可能预示不良临床结局。然而，ADMA在急性缺血性脑卒中后的确切作用仍需澄清。一方面，ADMA可能通过减少脑血流量而导致脑损伤。另一方面，ADMA可能参与NOS诱导的氧化应激和兴奋毒性神经元死亡。在本综述中，我们强调了目前的知识，从临床和实验研究ADMA及其作用的中风风险和缺血性脑损伤后的超急性期。最后，进一步的研究是必要的，以解开二甲基精氨酸与中风的密切关联的相关性。
Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, is known as mediator of endothelial cell dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. Accordingly, clinical studies found evidence that increased ADMA levels are associated with a higher risk of cerebrovascular events. After the acute event of ischemic stroke, levels of ADMA and its analog symmetric dimethylarginine (SDMA) are elevated through augmentation of protein methylation and oxidative stress. Furthermore, cleavage of ADMA through dimethylarginine dimethylaminohydrolases (DDAHs) is reduced. This increase of dimethylarginines might be predictive for adverse clinical outcome. However, the definite role of ADMA after acute ischemic stroke still needs to be clarified. On the one hand, ADMA might contribute to brain injury by reduction of cerebral blood flow. On the other hand, ADMA might be involved in NOS-induced oxidative stress and excitotoxic neuronal death. In the present review, we highlight the current knowledge from clinical and experimental studies on ADMA and its role for stroke risk and ischemic brain injury in the hyperacute stage after stroke. Finally, further studies are warranted to unravel the relevance of the close association of dimethylarginines with stroke.
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DOI：
10.1161/atvbaha.112.247726
发表时间：
2012-06
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Caplin B;Leiper J
通讯作者：
Leiper J
影响因子：
2.9
作者：
Chen, Mei-Fang;Li, Yuan-Jian;Xie, Xiu-Mei
通讯作者：
Xie, Xiu-Mei
影响因子：
3.8
作者：
Chen, Meifang;Li, Yuanjian;Xie, Xiumei
通讯作者：
Xie, Xiumei
影响因子：
4.8
作者：
Cardounel, AJ;Zweier, JL
通讯作者：
Zweier, JL
影响因子：
8.3
作者：
Dayoub, Hayan;Rodionov, Roman;Faraci, Frank M.
通讯作者：
Faraci, Frank M.