Effects of high glucose on vascular endothelial growth factor synthesis and secretion in aortic vascular smooth muscle cells from obese and lean zucker rats

Gabriella Doronzo, Michela Viretto, Isabella Russo, Luigi Mattiello, Giovanni Anfossi, Mariella Trovati

Research output: Contribution to journalArticlepeer-review

Abstract

Type 1 diabetes is characterized by insulin deficiency, type 2 by both insulin deficiency and insulin resistance: in both conditions, hyperglycaemia is accompanied by an increased cardiovascular risk, due to increased atherosclerotic plaque formation/instabilization and impaired collateral vessel formation. An important factor in these phenomena is the Vascular Endothelial Growth Factor (VEGF), a molecule produced also by Vascular Smooth Muscle Cells (VSMC). We aimed at evaluating the role of high glucose on VEGF-A164 synthesis and secretion in VSMC from lean insulin-sensitive and obese insulin-resistant Zucker rats (LZR and OZR). In cultured aortic VSMC from LZR and OZR incubated for 24 h with D-glucose (5.5, 15 and 25 mM) or with the osmotic controls L-glucose and mannitol, we measured VEGF-A164 synthesis (western, blotting) and secretion (western blotting and ELISA). We observed that: (i) D-glucose dose-dependently increases VEGF-A164 synthesis and secretion in VSMC from LZR and OZR (n = 6, ANOVA p = 0.002-0.0001); (ii) all the effects of 15 and 25 mM D -glucose are attenuated in VSMC from OZR vs. LZR (p = 0.0001); (iii) L-glucose and mannitol reproduce the VEGF-A164 modulation induced by D-glucose in VSMC from both LZR and OZR. Thus, glucose increases via an osmotic mechanism VEGF synthesis and secretion in VSMC, an effect attenuated in the presence of insulin resistance.

Original languageEnglish
Pages (from-to)9478-9488
Number of pages11
JournalInternational Journal of Molecular Sciences
Volume13
Issue number8
DOIs
Publication statusPublished - 2012

Keywords

  • Diabetes
  • Glucose
  • Insulin resistance
  • Lean Zucker rats
  • Obese zucker rats
  • Osmotic stress
  • Vascular endothelial growth factor
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Medicine(all)

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