title: Asymmetric dimethyarginine as marker and mediator in ischemic stroke.
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.
authors: Department of Neurology, Hannover Medical School, 30623 Hannover, Germany. worthmann.hans@mh-hannover.de.
authors: Shufen
authors: S
authors: Chen
authors: Na
authors: N
authors: Li
authors: Milani
authors: M
authors: Deb-Chatterji
authors: Qiang
authors: Q
authors: Dong
authors: Jan T
authors: JT
authors: Kielstein
authors: Karin
authors: K
authors: Weissenborn
authors: Hans
authors: H
authors: Worthmann
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase