title: High glucose-induced dysfunction of endothelial cells can be restored by HoxA9EC.
abstract: BACKGROUND
  High glucose (HG)-induced endothelial dysfunction is a common pathologic process of vascular disease in patients with diabetes. HoxA9EC is a transcriptional regulator of genes involved in the stabilization of endothelial function. We sought to elucidate the effect of HG on HoxA9EC expression in human umbilical venous endothelial cells (HUVECs), and the potential role of HoxA9EC in antagonizing HG-induced endothelial dysfunction.
  
  
  METHODS
  HUVECs treated with HoxA9EC transfection were cultured in media with HG, and those treated either by HG or HoxA9EC knockdown were incubated without HG. These cells were then subjected to experiments including mRNA expression analysis for eNOS, VEGFR-2, and HoxA9EC by quantitative RT-PCR; protein level analysis for eNOS, VEGFR-2, and HoxA9EC by Western blot; detection of nitric oxide (NO) concentration; and migration assay.
  
  
  RESULTS
  Expression levels of eNOS, VEGFR-2, and HoxA9EC, as well as cell migration and NO concentration, decreased rapidly in HUVECs with HoxA9EC knockdown or under HG conditions. Overexpression of HoxA9EC significantly repaired expression of eNOS and VEGFR-2, cell migration, and NO release of endothelial cells under HG conditions.
  
  
  CONCLUSIONS
  Inhibition of HoxA9EC induced by HG contributed to endothelial cell dysfunction, which could be rescued by augmentation of HoxA9EC under HG conditions.
authors.affiliation: Department of Endocrinology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China. doczkm@yahoo.com.cn
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.forename: Hongkun
authors.initials: H
authors.lastname: Zhang
authors.forename: Chunli
authors.initials: C
authors.lastname: Cao
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; C097899:homeobox protein HOXA9; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D040301:Vascular Endothelial Growth Factor Receptor-2; D005947:Glucose