Serum Levels of Protein-Bound Methylglyoxal-Derived Hydroimidazolone-1 are Independently Correlated with Asymmetric Dimethylarginine.

Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase, being involved in endothelial dysfunction. Furthermore, ADMA levels have been shown to predict future cardiovascular events in patients with coronary risk factors, such as diabetes and hypertension. We have previously found that glyceraldehyde-derived advanced glycation end products (glycer-AGEs) stimulate ADMA generation in vitro and the levels are associated with ADMA, endothelial dysfunction, and vascular inflammation in humans. However, it remains unclear what structurally distinct glycer-AGEs are independent correlates of ADMA. In this study, we addressed the issue. We measured serum levels of protein-bound and free methylglyoxal-derived hydroimidazolone-1 (MG-H1) and argpyrimidine, two major structurally identified glycer-AGEs by liquid chromatography-tandem mass spectrometry in 128 outpatients, and examined the correlations of these AGEs, vascular stiffness, and inflammation with ADMA. Moreover, we examined whether the changes in serum MG-H1 and argpyrimidine levels after 4-month treatment with oral hypoglycemic agents (OHAs) were associated with those of ADMA in other 44 patients with impaired glucose tolerance or type 2 diabetes. Multiple stepwise regression analysis revealed that protein-bound MG-H1, high-density lipoprotein cholesterol (inversely), high-sensitivity C-reactive protein, and cardio-ankle vascular index were independently correlated with ADMA (R2 = 0.259). Treatment with OHAs significantly decreased ADMA levels in 44 glucose-intolerant or type 2 diabetic patients, and the changes in protein-bound MG-H1 levels were positively associated with those in ADMA values (p < 0.05). This study demonstrates that serum levels of protein-bound MG-H1 are independently correlated with ADMA and may be a therapeutic target for cardiovascular disease.

• Authors: Nobuhiro Tahara, Ruchia Kojima, Risa Yoshida, Munehisa Bekki, Yoichi Sugiyama, Atsuko Tahara, Shoko Maeda, Akihiro Honda, Sachiyo Igata, Tomohisa Nakamura, Jiahui Sun, Takanori Matsui, Yoshihiro Fukumoto, Toshiro Matsui, Sho-Ichi Yamagishi
• Journal: Rejuvenation research (Rejuvenation Res) Vol. 22 Issue 5 Pg. 431-438 (Oct 2019) ISSN: 1557-8577 [Electronic] United States
• PMID: 30661488 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Glycation End Products, Advanced
• Hypoglycemic Agents
• Imidazoles
• imidazolone
• N,N-dimethylarginine
• Pyruvaldehyde
• Arginine

Topics

• Aged
• Arginine (analogs & derivatives, blood)
• Cross-Sectional Studies
• Diabetes Mellitus, Type 2 (blood, drug therapy, physiopathology)
• Female
• Glucose Intolerance (blood, drug therapy, physiopathology)
• Glycation End Products, Advanced (blood)
• Humans
• Hypoglycemic Agents (pharmacology)
• Imidazoles (blood)
• Inflammation (blood)
• Male
• Middle Aged
• Protein Binding
• Pyruvaldehyde (blood)
• Vascular Stiffness