Homoarginine and 3-nitrotyrosine in patients with takotsubo cardiomyopathy

摘要

In recent years, homoarginine was shown to be a cardiovascular risk factor [1], and to herald a poor prognosis in heart failure patients [2]. Yet, the underlying mechanism is elusive. Human and animal studies suggest that the enzyme responsible for the biosynthesis of homoarginine is arginine:glycine amidinotransferase (AGAT) [3-5]. Previously, excessive myocardial AGAT gene expression was observed in heart failure; the authors implicated AGAT in cardiac creatine synthesis [6]. This finding suggests that homoarginine synthesis in the myocardium may be elevated in heart failure. Thus far, there is no information about the homoarginine homeostasis in takotsubo cardiomyopathy (TTC) and which potential role this quite neglected non-proteinogenic amino acid may play in the development and recovery of TTC. In TTC patients we recently observed that the plasma concentration of asymmetric dimethylarginine (ADMA), another arginine homologue, is lower than the control, whereas the responsiveness to nitric oxide (NO) is substantially greater compared to healthy females [7]. This is of particular interest, because both L-arginine and L-homoarginine serve as substrates for NO synthases (NOS), while ADMA inhibits NOS-catalyzed production of NO from these substrates [8].