Dimethylarginine dimethylaminohydrolase: a new therapeutic target for the modulation of nitric oxide and angiogenesis.
Nitric oxide (NO) has a key role in promoting angiogenesis by increasing vasodilation, vascular permeability, endothelial cell proliferation and migration, and by modifying the activities of angiogenic mediators. NO is also critical for the mobilization of endothelial progenitor cells from the bone marrow which promotes vasculogenesis and angiogenesis. Studies have shown that the enzymes catalyzing NO synthesis are inhibited by the endogenously generated inhibitor asymmetric dimethylarginine (ADMA). Pharmacological agents targeted to modulate dimethyl-arginine dimethylaminohydrolase, the key enzyme metabolizing ADMA, may offer a potential strategy for developing novel pro- and anti-angiogenic therapies.
Singh
Jai Pal
JP
Eli Lilly and Co, Lilly Corporate Center, Indianapolis, IN 462865, USA. singh_jaipal@lilly.com
D000581:Amidohydrolases / Q000378:metabolism*; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D000581:Amidohydrolases; C059999:dimethylargininase