Amino Acids

, Volume 47, Issue 9, pp 1741–1750 | Cite as

Homoarginine in the shadow of asymmetric dimethylarginine: from nitric oxide to cardiovascular disease

  • Nikolaos Papageorgiou
  • Emmanuel Androulakis
  • Spyridon Papaioannou
  • Charalambos Antoniades
  • Dimitris TousoulisEmail author
Review Article
Part of the following topical collections:
  1. Homoarginine, Arginine and Relatives


It is well known that the endothelium maintains the vascular homeostasis. Importantly, endothelial dysfunction is regarded as a key early step in the development of atherosclerosis. Back in the early 1990s, it was found that asymmetric dimethylarginine (ADMA), an arginine metabolite derived from l-arginine (Arg) residues in proteins by asymmetric dimethylation on its guanidine group, is an endogenous inhibitor of nitric oxide (NO) synthase (NOS) isoforms. Inhibition of NO synthesis from Arg by the endothelial NOS isoform (eNOS) leads to endothelial dysfunction. Due to this action, ADMA participates in the pathophysiology of atherosclerosis and potentially contributes to cardiovascular events. Nowadays, homoarginine (hArg) is considered as a new key player in atherogenesis. hArg is a non-essential, non-proteinogenic amino acid which is synthesized from Arg by arginine:glycine amidinotransferase (AGAT). hArg is structurally related to Arg; formally, hArg is by one methylene (CH2) group longer than Arg, and may serve as a substrate for NOS, thus contributing to NO synthesis. For several decades, the pathophysiological role of hArg has been entirely unknown. hArg has been in the shadow of ADMA. Clinical studies have sought to investigate the relationship between circulating hArg levels and human disease states as well as cardiovascular prognosis. Recent studies indicate that hArg is actively involved in the vascular homeostasis, yet the underlying mechanisms are incompletely understood. In this article, we review the available literature regarding the role of ADMA and hArg in endothelial dysfunction and in cardiovascular disease as well as the possible associations between these endogenous Arg derivatives.


Asymmetric dimethylarginine l-Homoarginine Endothelial dysfunction Cardiovascular disease 



Asymmetric dimethylarginine


Arginineglycine amidinotransferase


Coronary artery disease


Cardiovascular disease


Dimethylarginine dimethylaminohydrolase


Flow-mediated dilatation


Guanidinoacetate methyltransferase




Intima-media thickness




Nitric oxide


NO synthase


Endothelial nitric oxide synthase


Neuronal nitric oxide synthase


Percutaneous coronary intervention


Protein arginine N-methyltransferases


Reactive oxygen species


Symmetric dimethylarginine


Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

This article does not contain any studies with human subjects or animals.


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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Nikolaos Papageorgiou
    • 1
  • Emmanuel Androulakis
    • 1
  • Spyridon Papaioannou
    • 1
  • Charalambos Antoniades
    • 1
  • Dimitris Tousoulis
    • 1
    Email author
  1. 1.1st Cardiology DepartmentAthens University Medical SchoolAthensGreece

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