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Asymmetric Dimethyarginine as Marker and Mediator in Ischemic Stroke
Department of Neurology, Hannover Medical School, 30623 Hannover, Germany
Department of Neurology, Huashan Hospital Fudan University, Shanghai 200040, China
Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 10050, China
Department of Nephrology and Hypertension, Hannover Medical School, 30623 Hannover, Germany
* Author to whom correspondence should be addressed.
Received: 28 September 2012; in revised form: 14 November 2012 / Accepted: 21 November 2012 / Published: 28 November 2012
Abstract: 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.
Keywords: asymmetric dimethylarginine (ADMA); symmetric dimethylarginine (SDMA); nitric oxide (NO); nitric oxide synthase (NOS); ischemic stroke
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Chen, S.; Li, N.; Deb-Chatterji, M.; Dong, Q.; Kielstein, J.T.; Weissenborn, K.; Worthmann, H. Asymmetric Dimethyarginine as Marker and Mediator in Ischemic Stroke. Int. J. Mol. Sci. 2012, 13, 15983-16004.
Chen S, Li N, Deb-Chatterji M, Dong Q, Kielstein JT, Weissenborn K, Worthmann H. Asymmetric Dimethyarginine as Marker and Mediator in Ischemic Stroke. International Journal of Molecular Sciences. 2012; 13(12):15983-16004.
Chen, Shufen; Li, Na; Deb-Chatterji, Milani; Dong, Qiang; Kielstein, Jan T.; Weissenborn, Karin; Worthmann, Hans. 2012. "Asymmetric Dimethyarginine as Marker and Mediator in Ischemic Stroke." Int. J. Mol. Sci. 13, no. 12: 15983-16004.