Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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Kr${\ddot}$ppel-Like Factor 2 Suppression by High Glucose as a Possible Mechanism of Diabetic Vasculopathy

  • Lee, Hae-Young (Cardiovascular Laboratory, Clinical Research Institute, Seoul National University Hospital) ;
  • Youn, Seock-Won (Cardiovascular Laboratory, Clinical Research Institute, Seoul National University Hospital) ;
  • Oh, Byung-Hee (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kim, Hyo-Soo (Cardiovascular Laboratory, Clinical Research Institute, Seoul National University Hospital)
  • Published : 2012.04.30
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Abstract

Background and Objectives: Endothelial dysfunction is widely observed in diabetes mellitus, resulting in diabetic vascular complications. Kr${\ddot}$ppel-like factor 2 (KLF2) is implicated as being a key molecule that maintains endothelial function. We evaluated the expression of KLF2 in endothelial cells cultured in high glucose and investigated its functional implication in a diabetic animal model. Subjects and Methods: Human umbilical vein endothelial cells (HUVECs) were cultured in physiologically high glucose (35 mM) condition. The Otsuka Long Evans Tokushima Fatty (OLETF) strain of rat was used as an excellent model of obese type II diabetes, and their lean littermates are Long Evans Tokushima Otsuka (LETO) rats. Results: In HUVECs cultured in physiologically high glucose condition, FOXO1 was activated whereas KLF2 and endothelial nitric oxide synthase (eNOS) expression was near completely abolished, which was completely reversed by FOXO1 small interfering ribonucleic acid. In the vessels harvested from the OLETF rats, the animal model of type II diabetes, KLF2 and eNOS expression were found depleted. When vascular remodeling was induced in the left common carotid artery by reduction of blood flow with partial ligation of the distal branches, greater neointimal hypertrophy was observed in OLETF rats compared with the control LETO rats. Conclusion: KLF2 suppression in endothelial cells by high glucose is a possible mechanism of diabetic endothelial dysfunction. The strategy of replenishing KLF2 may be effective for preventing diabetic vascular dysfunction.

Keywords

References

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