title: Dimethylarginine dimethylaminohydrolase-1 transgenic mice are not protected from ischemic stroke.
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).
  
  
  RESULTS
  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, neither brain tissue DDAH activity nor ADMA concentrations were different between TG and WT mice. In contrast, muscular DDAH activity was generally lower than in brain but significantly increased in TG mice.
  
  
  CONCLUSIONS
  Our study demonstrates that hDDAH-1 transgenic mice are not protected from ischemic cerebral tissue damage in tMCAO. This lack of protection is due to high basal cerebral DDAH activity, which is not further increasable by transgenic overexpression of DDAH.
authors.affiliation: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Leypoldt
authors.forename: Chi-Un
authors.initials: CU
authors.lastname: Choe
authors.forename: Mathias
authors.initials: M
authors.lastname: Gelderblom
authors.forename: Eike-Christin
authors.initials: EC
authors.lastname: von Leitner
authors.forename: Dorothee
authors.initials: D
authors.lastname: Atzler
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Christian
authors.initials: C
authors.lastname: Gerloff
authors.forename: Karsten
authors.initials: K
authors.lastname: Sydow
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.forename: Tim
authors.initials: T
authors.lastname: Magnus
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D005838:Genotype; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007511:Ischemia / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D020521:Stroke / Q000235:genetics* / Q000517:prevention & control*
chemical_list: D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase