dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic strokedimethylarginine dimethylaminohydrolase-1转基因老鼠不免受缺血性中风.pdfVIP

Dimethylarginine Dimethylaminohydrolase-1 Transgenic Mice Are Not Protected from Ischemic Stroke 1 1 1 2 3 Frank Leypoldt , Chi-Un Choe , Mathias Gelderblom , Eike-Christin von Leitner , Dorothee Atzler , 3 1 2 ¨ 3 1 Edzard Schwedhelm , Christian Gerloff , Karsten Sydow , Rainer H. Boger , Tim Magnus * 1 Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 2 Department of Cardiology, Hamburg University Heart Center, Hamburg, Germany, 3 Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Abstract Background: Methylated arginines are endogenous analogues of L-arginine, the substrate for nitric oxide (NO) synthase. Asymmetric dimethylarginine (ADMA) interferes with NO formation, causing endothelial dysfunction. ADMA is a predictor of cardiovascular events and mortality in humans. It is eliminated primarily by enzymatic activity of dimethylarginine dimethylaminohydrolase (DDAH). Methodology/Principal Findings: We investigated whether human DDAH-1 (hDDAH-1) transgenicity protects from ischemic tissue damage in temporary middle cerebral artery occlusion (tMCAO) in mice. Infarct sizes did not significantly differ between hDDAH-1 transgenic (TG) mice and wild-type littermates (WT). As expected, ADMA plasma concentrations were significantly decreased, cerebral hDDAH expression and protein significantly increased in transgenic animals. Interestingly, n