title: Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues.
abstract: OBJECTIVE
  Hypercholesterolemia is a major risk factor for erectile dysfunction (ED), but the mechanisms are not completely understood. Vascular endothelial growth factor (VEGF) is reduced in rabbit corporal tissue with cholesterol feeding. VEGF signaling leads to the phosphorylation of Akt and endothelial nitric oxide synthase (p-Akt and p-eNOS).
  
  
  METHODS
  New Zealand White rabbits (n = 50) were fed a 1% cholesterol (n = 8, 8, 8, 4) or normal (n = 6, 6, 6, 4) diet for 2, 4.5, 7.5, and 12 weeks. Akt, p-Akt, and p-Akt/Akt were measured by enzyme-linked immunosorbent assay. Levels of eNOS, p-eNOS, and neuronal and inducible nitric oxide synthase (nNOS and iNOS) mRNA and protein were assessed by polymerase chain reaction and Western analysis.
  
  
  RESULTS
  Cholesterol feeding was associated with a significant decrease in p-Akt/Akt 2.16-fold (P < 0.05), 3.28-fold (P < 0.02), and 3.42-fold (P < 0.02) at 4.5, 7.5, and 12 weeks, respectively. The reduction in p-Akt/Akt with the cholesterol diet at 2 weeks was not significantly different, but the correlation between the duration of cholesterol feeding and the reduction in p-Akt/Akt was high (r( 2) = 0.858). eNOS protein or mRNA did not change with cholesterol feeding, but p-eNOS was significantly decreased at 4.5 weeks and all subsequent time points. nNOS mRNA and protein levels were decreased at 4.5 weeks and all subsequent time points, while iNOS was not different between groups.
  
  
  CONCLUSIONS
  Hypercholesterolemia results in decreased VEGF signaling and decreased levels of the active form of eNOS in corporal tissue. Levels of nNOS were reduced by a different mechanism. VEGF signaling may provide a target to modulate ED.
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University Medical Center, 508 Fulton Street, Durham, NC 27710, USA.
authors.forename: Donghua
authors.initials: D
authors.lastname: Xie
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Kontos
authors.forename: Craig F
authors.initials: CF
authors.lastname: Donatucci
authors.forename: Brian H
authors.initials: BH
authors.lastname: Annex
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002784:Cholesterol / Q000008:administration & dosage*; D002149:Energy Intake; D004797:Enzyme-Linked Immunosorbent Assay; D007172:Erectile Dysfunction / Q000209:etiology / Q000503:physiopathology; D006937:Hypercholesterolemia / Q000150:complications; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010413:Penis / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects*
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D051057:Proto-Oncogene Proteins c-akt