Suppression of 3-deoxyglucosone and heparin-binding epidermal growth factor-like growth factor mRNA expression by an aldose reductase inhibitor in rat vascular smooth muscle cells

Weiguo Li, Yoji Hamada, Eitaro Nakashima, Keiko Naruse, Hideki Kamiya, Noboru Akiyama, Hiroko Hirooka, Naoki Takahashi, Seikoh Horiuchi, Nigishi Hotta, Yutaka Oiso, Jiro Nakamura

Research output: Contribution to journalArticle

9 Scopus citations


Reactive carbonyl compounds and oxidative stress have been recently shown to up-regulate the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells (SMCs) produced by SMC themselves. Because the polyol pathway has been reported to influence the formation of carbonyl compounds and the oxidative stress in various cells, we conducted this study to investigate whether the polyol pathway affects HB-EGF expression along with the generation of carbonyl compounds and the oxidative stress in SMCs. We found that, compared with those cultured with 5.5mM glucose, SMCs cultured with 40mM glucose showed the accelerated thymidine incorporation, elevated levels of intracellular sorbitol, 3-deoxyglucosone (3-DG), advanced glycation end products (AGEs), and thiobarbituric acid-reactive substances (TBARS) along with the enhanced expression of HB-EGF mRNA. An aldose reductase inhibitor (ARI), SNK-860, significantly inhibited all of these abnormalities, while aminoguanidine suppressed 3-DG levels and HB-EGF mRNA expression independent of sorbitol levels. The results suggest that the polyol pathway may play a substantial role in SMC hyperplasia under hyperglycemic condition in part by affecting HB-EGF mRNA expression via the production of carbonyl compounds and oxidative stress.

Original languageEnglish (US)
Pages (from-to)370-376
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - Feb 6 2004



  • 3-Deoxyglucosone
  • Advanced glycation end products
  • Aldose reductase inhibitor
  • HB-EGF
  • Polyol pathway
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this