Krüppel-like factor 2 suppression by high glucose as a possible mechanism of diabetic vasculopathy

Hae Young Lee, Seock Won Youn, Byung Hee Oh, Hyo Soo Kim

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background and Objectives: Endothelial dysfunction is widely observed in diabetes mellitus, resulting in diabetic vascular complications. Krüppel-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.

Original languageEnglish (US)
Pages (from-to)239-245
Number of pages7
JournalKorean Circulation Journal
Volume42
Issue number4
DOIs
StatePublished - Apr 1 2012

    Fingerprint

Keywords

  • Diabetes mellitus
  • Endothelial cells
  • Krüppel-like factor 2

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this