Asymmetric dimethyarginine as marker and mediator in ischemic stroke

TY - JOUR

T1 - Asymmetric dimethyarginine as marker and mediator in ischemic stroke

AU - Chen, Shufen

AU - Li, Na

AU - Deb-Chatterji, Milani

AU - Dong, Qiang

AU - Kielstein, Jan T

AU - Weissenborn, Karin

AU - Worthmann, Hans

PY - 2012/11/28

Y1 - 2012/11/28

N2 - 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.

AB - 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.

KW - Animals

KW - Arginine

KW - Biomarkers

KW - Brain Ischemia

KW - Cerebrovascular Circulation

KW - Enzyme Inhibitors

KW - Humans

KW - Methylation

KW - Nitric Oxide Synthase

KW - Oxidative Stress

KW - Protein Processing, Post-Translational

KW - Stroke

KW - Journal Article

KW - Review

U2 - 10.3390/ijms131215983

DO - 10.3390/ijms131215983

M3 - SCORING: Journal article

C2 - 23443106

VL - 13

SP - 15983

EP - 16004

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 12

ER -