The endothelial ADMA/NO pathway in hypoxia-related chronic respiratory diseases.
Since its discovery, many adhere to the view that asymmetric dimethylarginine (ADMA), as an inhibitor of the synthesis of nitric oxide (NO), contributes to the pathogenesis of various diseases. Particularly, this is evident in disease of the cardiovascular system, in which endothelial dysfunction results in an imbalance between vasoconstriction and vasodilatation. Even if increased ADMA concentrations are closely related to an endothelial dysfunction, several studies pointed to a potential beneficial effect of ADMA, mainly in the context of angioproliferative disease such as cancer and fibrosis. Antiproliferative properties of ADMA independent of NO have been identified in this context. In particular, the regulation of ADMA by its degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) is the object of many studies. DDAH is discussed as a promising therapeutic target for the indirect regulation of NO. In hypoxia-related chronic respiratory diseases, this controversy discussion of ADMA and DDAH is particularly evident and is therefore subject of this review.
University Medical Center Hamburg-Eppendorf, Department of Clinical Pharmacology and Toxicology, Martinistraße 52, 20246 Hamburg, Germany.
Nicole
N
Lüneburg
University Medical Center Hamburg-Eppendorf, II Department of Medicine-Oncology, Hematology, Stem Cell Transplantation, Section of Pneumology, Hamburg, Germany.
Lars
0000-0002-9422-6195
L
Harbaum
University Medical Center Hamburg-Eppendorf, II Department of Medicine-Oncology, Hematology, Stem Cell Transplantation, Section of Pneumology, Hamburg, Germany ; The Vera Moulton Wall Center for Pulmonary Vascular Disease and Cardiovascular Institute, Stanford University - School of Medicine, Stanford, USA.
Jan K
0000-0002-7784-8267
JK
Hennigs
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D002908:Chronic Disease; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D012140:Respiratory Tract Diseases / Q000378:metabolism*
D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase