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

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-kappaB) inhibited endothelial cell migration (P < 0.05). High glucose induced NF-kappa B DNA binding activity may mediate this inhibition of migration by regulating intracellular nitric oxide. In Nitro wound heating 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-kappa B inhibitors (including E3-4-methylphenyl sulfonyl-2-propenenitrile, N-tosyl-Lys-chloromethylketone (TLCK), or over-expression of inhibitor subunit of kappa B) and endothelial nitric oxide synthase inhibitors (N-methyl-L-arginine (L-NMMA) and Nw-nitro-L-arginine methyl ester (L-NAME)), Furthermore, NF-kappa B 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-kappa B and NO in differences observed in migration. In summary our results for the first time suggest therapeutic strategies invoking inhibition of NF-kappa B activation induced by high glucose. which may improve wound healing and help avoid some of the vascular complications of diabetes. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.