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