title: Effects of high glucose on human cavernous endothelial cells.
abstract: OBJECTIVE
  To obtain experimental evidence for a causal effect of high glucose (HG) on cavernous endothelial dysfunction.
  
  
  METHODS
  Cavernous tissues were obtained from patients undergoing surgery for penile prosthesis implantation. Endothelial cells were isolated by binding to anti-CD31 antibody, followed by magnetic capture. Their endothelial identity was verified by flow cytometry and immunofluorescence staining for endothelial markers CD31, von Willebrand factor, and endothelial nitric oxide synthase, and by their ability to form tube-like structures in matrigel (tube formation) and to endocytose acetylated low-density lipoprotein (low-density lipoprotein uptake). The cells were then cultured under normal glucose (NG) (5 mM) or HG (25 mM) conditions, followed by analysis for endothelial gene expression, function, proliferation, apoptosis, and mitochondrial fragmentation.
  
  
  RESULTS
  Human cavernous endothelial cell (HCEC) strains were established and determined to be nearly 100% pure endothelial cells. In the HG culture condition, HCECs expressed approximately 50% less CD31, von Willebrand factor, and endothelial nitric oxide synthase, but nearly twice as much collagen IV compared with HCECs grown in NG medium. HG also suppressed low-density lipoprotein uptake and tube formation by approximately 50%. HCECs grew significantly slower in the high-glucose medium than in the NG medium. Approximately 3 times as many cells exhibited apoptosis in the HG medium as in the NG medium. Approximately 4 times as many cells contained fragmented mitochondria in the HG medium as in the NG medium.
  
  
  CONCLUSIONS
  HG caused a decrease in endothelial proliferation, function, and marker expression. It also caused an increase in endothelial collagen IV expression, apoptosis, and mitochondrial fragmentation. Together, these HG-induced changes in cavernous endothelial cells provide an explanation for hyperglycemia's detrimental effects on erectile function.
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, School of Medicine, San Francisco, CA 94143-0738, USA.
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Ning
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Qiu
authors.forename: Lia
authors.initials: L
authors.lastname: Baine
authors.forename: Guiting
authors.initials: G
authors.lastname: Lin
authors.forename: Tom F
authors.initials: TF
authors.lastname: Lue
authors.forename: Ching-Shwun
authors.initials: CS
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D007172:Erectile Dysfunction / Q000139:chemically induced / Q000473:pathology*; D005434:Flow Cytometry; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008297:Male; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D003470:Culture Media; D013549:Sweetening Agents; D005947:Glucose