Homoarginine in the renal and cardiovascular systems

Abstract

Homoarginine (hArg) is an endogenous, nonproteinogenic amino acid which differs from arginine by an additional methylene (CH2) group in the backbone. In this brief narrative review, we summarize the current literature on hArg in the renal and cardiovascular systems. Epidemiological studies have identified low hArg levels as an independent risk marker for cardiovascular, cerebrovascular, and renal diseases as well as for mortality. The relatively low correlation of hArg with established cardiovascular risk factors underlines its great potential as an emerging biomarker to improve risk prediction because plasma hArg concentrations might reflect previously unrecognized pathophysiological processes. hArg may be involved in the pathogenesis of various diseases due to its effects on nitric oxide (NO) and energy metabolism. In view of its structural similarities with arginine, it has been proposed that hArg impacts on arginine metabolism and subsequently also on NO synthesis. The key enzyme for hArg synthesis, arginine:glycine amidinotransferase (AGAT), is involved in the synthesis of energy metabolites including guanidinoacetate, the precursor of creatine. Therefore, the involvement of hArg in energy metabolism could partially explain the close association between hArg and cardiovascular diseases such as heart failure. Whether hArg supplementation or modification of key enzymes of hArg metabolism such as AGAT activity is effective for the treatment of chronic diseases remains to be elucidated.

Low Homoarginine Levels in the Prognosis of Patients With Acute Chest Pain

“…Low circulating concentrations of the endogenous amino acid homoarginine have been reported to be a prognostic marker for mortality and cardiovascular events in a variety of diseases, among them heart failure, stroke, and CKD 1, 2. In the present study sample of patients with acute chest pain, median plasma homoarginine was 2.38 [1.86–3.01] μmol/L.…”

“…During the last 5 years, several studies indicated that low concentrations of the naturally occurring amino acid homoarginine predict a risk of adverse cardio‐ and cerebrovascular outcome and of mortality (reviewed in previous works1, 2). Analyses of the associated clinical phenotypes, as well as experimental studies in mice, have proven a mechanistic link of impaired homoarginine and cerebrovascular disease 3.…”

Serum and cerebrospinal fluid concentrations of homoarginine, arginine, asymmetric and symmetric dimethylarginine, nitrite and nitrate in patients with multiple sclerosis and neuromyelitis optica

“…Changes in NO bioavailability and in circulating ADMA, SDMA and hArg concentrations have been intensively studied in cardiovascular diseases (CVD) in recent decades establishing high ADMA and low hArg concentrations as cardiovascular risk factors associated with cardiovascular and all-cause mortality (Böger et al 2009;März et al 2010;Pilz et al 2011;Drechsler et al 2011;Choe et al 2013;Atzler et al 2013Atzler et al , 2014Pilz et al 2014Pilz et al , 2015a. Moreover, recent studies on rheumatoid arthritis have demonstrated a positive association of inflammatory burden with ADMA levels independent of classical CVD risk factors (Sandoo et al 2014), suggesting a pivotal role of altered NO metabolism in chronic inflammatory diseases.…”

The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

“…hArg has been reported to be a substrate for NOS as well (Moali et al 1998) and may therefore affect NOdependent endothelial function (Valtonen et al 2008). Low concentrations of hArg are positively associated with cardiovascular and all-cause mortality as well as cardiovascular diseases in humans (März et al 2010;Pilz et al 2011Pilz et al , 2014Pilz et al , 2015.…”