L-homoarginine and cardiovascular disease

TY - JOUR

T1 - L-homoarginine and cardiovascular disease

AU - Atzler, Dorothee

AU - Schwedhelm, Edzard

AU - Choe, Chi-un

PY - 2015/1/1

Y1 - 2015/1/1

N2 - PURPOSE OF REVIEW: An increasing number of reports indicate that low levels of the endogenous amino acid L-homoarginine are linked to cardiovascular disease. In this article, we review the current findings regarding L-homoarginine metabolism and (patho-)physiology with a focus on its clinical impact.RECENT FINDINGS: Recent clinical and epidemiological studies revealed a strong association of low circulating L-homoarginine with cardiovascular outcomes and mortality. Human and murine studies identified L-arginine:glycine amidinotransferase (AGAT) as the responsible enzyme for endogenous L-homoarginine formation, suggesting a further important function of AGAT apart from its involvement in creatine and energy metabolism. Further studies related L-homoarginine to smoking and hypertension, and metabolic phenotypes.SUMMARY: AGAT deficiency results in diminished intracellular energy stores (i.e., ATP and phosphocreatine), as well as a lack of L-homoarginine, and has been linked to an improved metabolic risk profile, but also to impaired cardiac and cerebrovascular function. L-homoarginine's structural similarity to L-arginine suggested physiological interference with L-arginine pathways (e.g., nitric oxide). Animal experiments and clinical trials are needed to improve knowledge on the physiology of L-homoarginine and differentiate its role as marker and mediator in cardiovascular disease.

AB - PURPOSE OF REVIEW: An increasing number of reports indicate that low levels of the endogenous amino acid L-homoarginine are linked to cardiovascular disease. In this article, we review the current findings regarding L-homoarginine metabolism and (patho-)physiology with a focus on its clinical impact.RECENT FINDINGS: Recent clinical and epidemiological studies revealed a strong association of low circulating L-homoarginine with cardiovascular outcomes and mortality. Human and murine studies identified L-arginine:glycine amidinotransferase (AGAT) as the responsible enzyme for endogenous L-homoarginine formation, suggesting a further important function of AGAT apart from its involvement in creatine and energy metabolism. Further studies related L-homoarginine to smoking and hypertension, and metabolic phenotypes.SUMMARY: AGAT deficiency results in diminished intracellular energy stores (i.e., ATP and phosphocreatine), as well as a lack of L-homoarginine, and has been linked to an improved metabolic risk profile, but also to impaired cardiac and cerebrovascular function. L-homoarginine's structural similarity to L-arginine suggested physiological interference with L-arginine pathways (e.g., nitric oxide). Animal experiments and clinical trials are needed to improve knowledge on the physiology of L-homoarginine and differentiate its role as marker and mediator in cardiovascular disease.

U2 - 10.1097/MCO.0000000000000123

DO - 10.1097/MCO.0000000000000123

M3 - SCORING: Journal article

C2 - 25474016

VL - 18

SP - 83

EP - 88

JO - CURR OPIN CLIN NUTR

JF - CURR OPIN CLIN NUTR

SN - 1363-1950

IS - 1

ER -