Pyridoxine restores endothelial cell function in high glucose

Metab Syndr Relat Disord. 2011 Feb;9(1):63-8. doi: 10.1089/met.2010.0085. Epub 2010 Oct 30.

Abstract

Objective: Aminoguanidine, which inhibits the formation of advanced glycosylation end products, can restore the ability of endothelial cells to align and elongate in response to shear stress when that ability is lost during culture in high glucose conditions. This study tests whether aminoguanidine can also restore migratory ability of endothelial cells and whether pyridoxine, a stable form of vitamin B6, can restore migratory ability and ability to align and elongate in response to shear.

Methods: Human aortic endothelial cells were cultured in normal glucose (5.5 mM), 17.5 mM glucose, and 30.5 mM glucose in the presence or absence of 5 mM aminoguanidine or varying concentrations of pyridoxine (10-1,000 mg/L). Assay of percent closure of a scrape wound after 24 h quantified migratory ability, and alignment and elongation under flow at 10 dynes/cm(2) quantified response to shear stress.

Results: Aminoguanidine (5 mM) fully restores and pyridoxine (100 mg/L, 0.6 μM) partially restores migratory ability of cells cultured in 30.5 mM glucose. Pyridoxine (100 mg/L) fully restores the migratory ability of cells cultured in 17.5 mM glucose. Pyridoxine (100 mg/L) fully restores endothelial cell alignment and elongation and response to shear stress at 30.5 mM glucose.

Conclusions: Pyridoxine, at dosages known to be safe from previous studies (<250 mg/day) can restore migratory ability and shear stress response to endothelial cells cultured in high-glucose conditions. This indicates that pyridoxine is a potential candidate for treatment of diabetic ulcers and atherosclerosis in diabetes due to the link between these pathologies and endothelial dysfunction in diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aorta / cytology
  • Cell Movement / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Endothelial Cells / drug effects*
  • Endothelial Cells / physiology*
  • Glucose / adverse effects
  • Glucose / pharmacology*
  • Guanidines / pharmacology
  • Humans
  • Pyridoxine / pharmacology*
  • Wound Healing / drug effects
  • Wound Healing / physiology

Substances

  • Guanidines
  • Glucose
  • Pyridoxine
  • pimagedine