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Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues.

Publication ,  Journal Article
Xie, D; Kontos, CD; Donatucci, CF; Annex, BH
Published in: J Sex Med
September 2005

PURPOSE: 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). MATERIAL AND 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.

Duke Scholars

Published In

J Sex Med

DOI

ISSN

1743-6095

Publication Date

September 2005

Volume

2

Issue

5

Start / End Page

634 / 640

Location

Netherlands

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rabbits
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Penis
  • Obstetrics & Reproductive Medicine
  • Nitric Oxide Synthase
 

Citation

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MLA
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Xie, D., Kontos, C. D., Donatucci, C. F., & Annex, B. H. (2005). Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues. J Sex Med, 2(5), 634–640. https://doi.org/10.1111/j.1743-6109.2005.00111.x
Xie, Donghua, Christopher D. Kontos, Craig F. Donatucci, and Brian H. Annex. “Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues.J Sex Med 2, no. 5 (September 2005): 634–40. https://doi.org/10.1111/j.1743-6109.2005.00111.x.
Xie D, Kontos CD, Donatucci CF, Annex BH. Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues. J Sex Med. 2005 Sep;2(5):634–40.
Xie, Donghua, et al. “Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues.J Sex Med, vol. 2, no. 5, Sept. 2005, pp. 634–40. Pubmed, doi:10.1111/j.1743-6109.2005.00111.x.
Xie D, Kontos CD, Donatucci CF, Annex BH. Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues. J Sex Med. 2005 Sep;2(5):634–640.
Journal cover image

Published In

J Sex Med

DOI

ISSN

1743-6095

Publication Date

September 2005

Volume

2

Issue

5

Start / End Page

634 / 640

Location

Netherlands

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rabbits
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Penis
  • Obstetrics & Reproductive Medicine
  • Nitric Oxide Synthase