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A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits.

Publication ,  Journal Article
Xie, D; Findley, CM; Greenfield, JM; Pippen, AM; Kontos, CD; Donatucci, CF; Annex, BH
Published in: J Sex Med
September 2008

INTRODUCTION: Hypercholesterolemia causes a decrease in normal corporal tissue vasoreactivity in a preclinical model of erectile dysfunction. Previous studies have shown that intracorporal injection (ICI) of basic fibroblast growth factor (bFGF) reverses some of the detrimental vasoreactivity effects of hypercholesterolemia and increases vascular endothelial growth factor (VEGF) expression. AIM: We sought to determine whether the beneficial effects of bFGF are VEGF-mediated. METHODS: A total of 32 New Zealand white rabbits were fed a 1% cholesterol diet for 6 weeks and randomly divided into four groups (N = 8/group). Group 1 received a 2.5 microg bFGF ICI and 2.5 x 10(11) viral particle unit (vpu) of adenovirus encoding beta-galactosidase (Ad beta-gal) ICI, 10 days later. Group 2 received a 2.5 microg bFGF ICI and 2.5 x 10(11) vpu of adenovirus encoding soluble VEGF receptor (VEGFR) (AdsVEGFR, a VEGF trap) ICI, 10 days later. Group 3 received phosphate buffered saline solution (PBS) ICI and 2.5 x 10(11) vpu Ad beta-gal ICI, 10 days later. Group 4 received PBS ICI and 2.5 x 10(11) vpu AdsVEGFR ICI, 10 days later. MAIN OUTCOME MEASURES: The corpus cavernosum was harvested for vasoreactivity studies 10 days post viral injection. The effective dose of 50% maximum relaxation was determined. VEGF levels were assessed by enzyme-linked immunosorbent assay. Total and phosphorylated Akt and endothelial nitric oxide were analyzed by Western blot. RESULTS: Endothelium-dependent vasoreactivity was significantly greater in Group 1 vs. all other groups. The VEGF trap eliminated the beneficial effects of bFGF on endothelium-dependent vasoreactivity and decreased Akt and nitric oxide phosphorylation. CONCLUSIONS: These data demonstrate that VEGF activity contributes much of the therapeutic modulation of bFGF-mediated vasoreactivity in corporal tissue.

Duke Scholars

Published In

J Sex Med

DOI

EISSN

1743-6109

Publication Date

September 2008

Volume

5

Issue

9

Start / End Page

2069 / 2078

Location

Netherlands

Related Subject Headings

  • Vasodilation
  • Vascular Endothelial Growth Factor A
  • Recombinant Proteins
  • Receptors, Vascular Endothelial Growth Factor
  • Rabbits
  • Proto-Oncogene Proteins c-akt
  • Penis
  • Obstetrics & Reproductive Medicine
  • Nitric Oxide Synthase Type III
  • Male
 

Citation

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Xie, D., Findley, C. M., Greenfield, J. M., Pippen, A. M., Kontos, C. D., Donatucci, C. F., & Annex, B. H. (2008). A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits. J Sex Med, 5(9), 2069–2078. https://doi.org/10.1111/j.1743-6109.2008.00933.x
Xie, Donghua, Clarence M. Findley, Jason M. Greenfield, Anne M. Pippen, Christopher D. Kontos, Craig F. Donatucci, and Brian H. Annex. “A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits.J Sex Med 5, no. 9 (September 2008): 2069–78. https://doi.org/10.1111/j.1743-6109.2008.00933.x.
Xie D, Findley CM, Greenfield JM, Pippen AM, Kontos CD, Donatucci CF, et al. A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits. J Sex Med. 2008 Sep;5(9):2069–78.
Xie, Donghua, et al. “A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits.J Sex Med, vol. 5, no. 9, Sept. 2008, pp. 2069–78. Pubmed, doi:10.1111/j.1743-6109.2008.00933.x.
Xie D, Findley CM, Greenfield JM, Pippen AM, Kontos CD, Donatucci CF, Annex BH. A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits. J Sex Med. 2008 Sep;5(9):2069–2078.
Journal cover image

Published In

J Sex Med

DOI

EISSN

1743-6109

Publication Date

September 2008

Volume

5

Issue

9

Start / End Page

2069 / 2078

Location

Netherlands

Related Subject Headings

  • Vasodilation
  • Vascular Endothelial Growth Factor A
  • Recombinant Proteins
  • Receptors, Vascular Endothelial Growth Factor
  • Rabbits
  • Proto-Oncogene Proteins c-akt
  • Penis
  • Obstetrics & Reproductive Medicine
  • Nitric Oxide Synthase Type III
  • Male