The DDAH/ADMA pathway in the control of endothelial cell migration and angiogenesis.
ADMA (asymmetric dimethylarginine) is a cardiovascular risk factor and an endogenous inhibitor of NOS (nitric oxide synthase). ADMA is metabolized by DDAHs (dimethylarginine dimethylaminohydrolases). ADMA levels are increased in cardiovascular disorders associated with abnormal angiogenesis but the mechanisms are poorly understood. Recent studies show that altering ADMA metabolism in vivo and in vitro modulates the activity of Rho GTPases, key regulators of actin dynamics, endothelial cell motility and angiogenesis. In the present review, we consider this and other NO-dependent and -independent molecular mechanisms by which the DDAH/ADMA pathway regulates angiogenesis.
Fiedler
Lorna R
LR
Department of Clinical Pharmacology and Therapeutics, BHF Laboratories, 5 University Street, Rayne Institute, University College London, London WC1E 6JJ, UK.
Wojciak-Stothard
Beata
B
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase; D020741:rho GTP-Binding Proteins