The DDAH/ADMA pathway is a critical regulator of NO signalling in vascular homeostasis.
NO is an important regulator of cardiovascular remodelling and function. ADMA, an endogenous L-arginine analogue, reduces NO production by inhibiting the activity of NOS. ADMA levels in turn, are regulated by DDAH, which metabolises ADMA. High levels of ADMA and dysregulated DDAH activity are risk factors for cardiovascular disease and morbidity. To investigate this link, the DDAH I null mouse has been recently generated and has a lethal phenotype. Studies on vascular function in the DDAH I heterozygous knockout mouse, which is viable, demonstrates a causal link between reduced DDAH I activity, increased ADMA levels and reduced NO signalling and vascular dysfunction. In another study, detailed in vitro analyses reveal that the DDAH/ADMA pathway critically regulates endothelial cell motility and angiogenesis and establishes some of the molecular mechanisms involved. These studies highlight the importance of DDAH and ADMA in regulating NO dependent vascular homeostasis.
Fiedler
Lorna
L
Rayne Institute, Clinical Pharmacology, University College London, London, UK. l.fiedler@ucl.ac.uk
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D006706:Homeostasis; D009569:Nitric Oxide / Q000378:metabolism*; D015398:Signal Transduction
C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase