High glucose induced nuclear factor kappa B mediated inhibition of endothelial cell migration

Masao Hamuro, Jodie Polan, Mohan Natarajan, Sumathy Mohan

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

Delayed wound healing and accelerated atherosclerosis are common vascular complications of diabetes mellitus. Although elevated blood glucose level is the major contributing factor, mechanisms that mediate these complications are not clearly understood. In the present study, we have demonstrated that elevated glucose inhibits endothelial cell migration, thereby delaying wound healing. Our results clearly indicated that high glucose (10 or 30 mM) induced activation of nuclear factor kappa B (NF-κB) inhibited endothelial cell migration (P<0.05). High glucose induced NF-κB DNA binding activity may mediate this inhibition of migration by regulating intracellular nitric oxide. In vitro wound healing model in human aortic endothelial cells (HAEC) were used to evaluate cell migration under the influence of high glucose. The migration inhibited by high glucose was restored by NF-κB inhibitors (including E3-4-methylphenyl sulfonyl-2-propenenitrile, N-tosyl-Lys-chloromethylketone (TLCK), or over-expression of inhibitor subunit of κB) and endothelial nitric oxide synthase inhibitors (N-methyl-L-arginine (L-NMMA); and Nω-nitro-L-arginine methyl ester (L-NAME)). Furthermore, NF-κB inhibitors attenuated high glucose induced eNOS expression and intracellular nitric oxide (NO) production. Cytoskeletal immunofluorescence staining confirmed differences in actin distribution in HAEC incubated in high glucose in the presence or absence of NF-κB and NO inhibitors, explaining the differences observed in migration. In summary, our results for the first time suggest therapeutic strategies involving inhibition of NF-κB activation induced by high glucose, which may improve wound healing and help avoid some of the vascular complications of diabetes.

Original languageEnglish (US)
Pages (from-to)277-287
Number of pages11
JournalAtherosclerosis
Volume162
Issue number2
DOIs
StatePublished - May 13 2002

Keywords

  • Endothelial cell
  • NF-κB
  • NO wound healing and migration

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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