title: High cholesterol feeding in C57/Blc6 mice alters expression within the VEGF receptor-ligand family in corporal tissue.
abstract: BACKGROUND
  Angiogenesis, the growth and proliferation of blood vessels from existing vascular structures, is mediated by many cytokine growth factors and receptors, among the most important are the vascular endothelial growth factor (VEGF) family.
  
  
  OBJECTIVE
  Decreases in VEGF receptor signaling have been linked to abnormalities in vasoreactivity in corporal tissue, but it is unknown if alterations in the VEGF ligands and/or receptors contribute to this process.
  
  
  METHODS
  We sought to determine changes in vasoreactivity and the expression of the family of VEGF ligands and receptors in corporal tissue with cholesterol feeding in C57BL6 mice. Methods. Twenty-four mice (N = 8/group) were fed a normal diet (Group 1) or a 1.25% high cholesterol diet for 4 (Group 2) or 12 (Group 3) weeks. Isometric tension studies were performed on corporal strips and dose response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivities. Levels of VEGF-A, B, C, D, VEGF receptors (VEGFRs) were detected by PCR (polymerase chain reaction) and/or western blot/enzyme-linked immunosorbent assay (ELISA). Endothelial and smooth muscle cell contents were determined by immunohistochemistry.
  
  
  RESULTS
  At 4 weeks there was a small but significant decrease in endothelium-dependent vasoreactivity. Both mRNA and protein levels of VEGFR-1 were decreased, while VEGF-B was increased in Group 2 vs. Group 1, with no change in VEGF-A or endothelial cell content. By 12 weeks, decreases in both endothelium-dependent and endothelium-independent vasoreactivity were evident with decrease in most VEGF ligands (except VEGF-B), receptors, and receptor signaling.
  
  
  CONCLUSIONS
  Cholesterol feeding in C57BL6 mice results in alterations in the VEGF receptor-ligand family that may initially serve to limit the degree of vascular injury but these adaptations fail with the continuation of cholesterol feeding.
authors.affiliation: Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Donghua
authors.initials: D
authors.lastname: Xie
authors.affiliation: Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Surovi
authors.initials: S
authors.lastname: Hazarika
authors.affiliation: Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Andrich
authors.affiliation: Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Mike E
authors.initials: ME
authors.lastname: Padgett
authors.affiliation: Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Kontos
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC.
authors.forename: Craig F
authors.initials: CF
authors.lastname: Donatucci
authors.affiliation: Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC;. Electronic address: annex001@mc.duke.edu.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Annex
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010413:Penis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*
chemical_list: D002791:Cholesterol, Dietary; D012333:RNA, Messenger; D002784:Cholesterol; D040262:Receptors, Vascular Endothelial Growth Factor; D006152:Cyclic GMP