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

Donghua Xie, Clarence M. Findley, Jason M. Greenfield, Anne M. Pippen, Christopher D. Kontos, Craig F. Donatucci, Brian H. Annex

Research output: Contribution to journalArticle

Abstract

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 μg bFGF ICI and 2.5 × 1011 viral particle unit (vpu) of adenovirus encoding β-galactosidase (Adβ-gal) ICI, 10 days later. Group 2 received a 2.5 μg bFGF ICI and 2.5 × 1011 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 × 1011 vpu Adβ-gal ICI, 10 days later. Group 4 received PBS ICI and 2.5 × 1011 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 phoshorylated 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.

Original languageEnglish (US)
Pages (from-to)2069-2078
Number of pages10
JournalJournal of Sexual Medicine
Volume5
Issue number9
DOIs
StatePublished - Jan 1 2008

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Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Rabbits
Injections
Virion
Adenoviridae
Galactosidases
Hypercholesterolemia
Sodium Chloride
Endothelium
Nitric Oxide
Phosphates
Vascular Endothelial Growth Factor Receptor
Erectile Dysfunction
Western Blotting
Enzyme-Linked Immunosorbent Assay
Cholesterol
Phosphorylation
Outcome Assessment (Health Care)
Diet

Keywords

  • Cytokine Growth Factors
  • Endothelium
  • Nitric Oxide

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits. / Xie, Donghua; Findley, Clarence M.; Greenfield, Jason M.; Pippen, Anne M.; Kontos, Christopher D.; Donatucci, Craig F.; Annex, Brian H.

In: Journal of Sexual Medicine, Vol. 5, No. 9, 01.01.2008, p. 2069-2078.

Research output: Contribution to journalArticle

Xie, Donghua ; Findley, Clarence M. ; Greenfield, Jason M. ; Pippen, Anne M. ; Kontos, Christopher D. ; Donatucci, Craig F. ; Annex, Brian H. / A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits. In: Journal of Sexual Medicine. 2008 ; Vol. 5, No. 9. pp. 2069-2078.
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AU - Xie, Donghua

AU - Findley, Clarence M.

AU - Greenfield, Jason M.

AU - Pippen, Anne M.

AU - Kontos, Christopher D.

AU - Donatucci, Craig F.

AU - Annex, Brian H.

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AB - 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 μg bFGF ICI and 2.5 × 1011 viral particle unit (vpu) of adenovirus encoding β-galactosidase (Adβ-gal) ICI, 10 days later. Group 2 received a 2.5 μg bFGF ICI and 2.5 × 1011 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 × 1011 vpu Adβ-gal ICI, 10 days later. Group 4 received PBS ICI and 2.5 × 1011 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 phoshorylated 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.

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