ADMA (asymmetric dimethylarginine) and angiogenic potential in patients with type 2 diabetes and prediabetes

Exp Biol Med (Maywood). 2021 Jan;246(2):153-162. doi: 10.1177/1535370220959738. Epub 2020 Sep 22.

Abstract

Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase and marker of endothelial dysfunction, but the question remains as to whether asymmetric dimethylarginine is a marker of cardiovascular episodes or their independent risk factor. ADMA/DDAH (dimethylaminohydrolase) pathway regulates vascular endothelial growth factor (VEGF)-mediated angiogenesis due to its impact on the NO formation. The aim of the study was to assess the concentrations of asymmetric dimethylarginine and the angiogenic potential in the blood of subjects with type 2 diabetes (T2DM, n = 33) and patients with prediabetes (n = 32)-impaired fasting glycemia and/or impaired glucose tolerance (WHO criteria). The study found that both the prediabetes group and subjects with T2DM had significantly elevated concentrations of asymmetric dimethylarginine, significantly high levels of VEGF-A, low ratio of sVEGF-R1/VEGF-A, and sVEGF-R2/VEGF-A. This may suggest endothelial damage at early stages of carbohydrate metabolism dysfunction-before T2DM is diagnosed. Higher proangiogenic potential in prediabetes and T2DM patients than in healthy subjects, is not only the effect of an increase in VEGF-A levels, but also reduced inhibition of circulating receptors.

Keywords: Endothelial dysfunction; angiogenesis; asymmetric dimethylarginine; growth factors; prediabetes; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neovascularization, Physiologic / drug effects*
  • Prediabetic State / physiopathology*
  • Solubility
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • N,N-dimethylarginine
  • Arginine
  • Vascular Endothelial Growth Factor Receptor-1