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Asymmetric dimethylarginine (ADMA): an endogenous inhibitor of angiogenesis

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Abstract

Endothelium-derived nitric oxide (NO) plays a critical role in angiogenesis. The angiogenic effects of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and other growth factors are mediated to a significant degree by their stimulation of NO release. Angiogenic processes known to be dependent upon NO release include endothelial cell survival, proliferation, migration, and interaction with the extracellular matrix, as well as mobilization of endothelial progenitor cells from the bone marrow. Pharmacological inhibition or genetic disruption of the NO synthase pathway interfere with angiogenesis. Because it is a competitive antagonist of NO synthase, asymmetric dimethylarginine (ADMA) also acts as an endogenous inhibitor of angiogenesis. Conditions that increase plasma ADMA levels impair angiogenesis, whereas therapeutic measures to counteract the influence of ADMA enhance angiogenesis. Manipulation of ADMA generation or metabolism may represent a new therapeutic approach for angiogenesis-related disorders.

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Acknowledgements

This work was supported by grants from the National Heart, Lung and Blood Institute (R01 HL-63685; R01AT/HL00204; P01 AG18784; and PO1AI50153); by NIH grant M01 RR 00070 (General Clinical Research Center, Stanford University School of Medicine); by a National Research Service Award T32 HL07708 from the NHLBI; by Philip Morris USA Inc; and by the Tobacco Related Disease Research Program (7RT-0128).

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  1. Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA

    John P. Cooke

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Cooke, J.P. Asymmetric dimethylarginine (ADMA): an endogenous inhibitor of angiogenesis. Eur J Clin Pharmacol 62 (Suppl 1), 115–121 (2006). https://doi.org/10.1007/s00228-005-0005-y

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