title: Application of angiogenic factors for therapy of erectile dysfunction: protein and DNA transfer of VEGF 165 into the rat penis.
abstract: OBJECTIVE
  To establish a laboratory animal model for vascular endothelial growth factor (VEGF) transfer in the rat penis to invent a curative therapy for erectile dysfunction (ED). Vascular insufficiency is a common pathomechanism of ED. Previous investigations have shown neovascularization of ischemic organs after gene transfer of VEGF.
  
  
  METHODS
  For VEGF-protein transfer, osmotic pumps were connected to the renal arteries of rats. The pumps were filled with human VEGF 165 protein (n = 20) or sterile saline (n = 20). After 28 days, a VEGF serum immunoassay was performed to document successful delivery. For VEGF-DNA transfer, liposome complexes containing VEGF 165 expression vectors were injected into rat corpora cavernosa. After immunostaining, computerized image analysis was performed to quantify the percentage of area (within the corpora cavernosa) covered by smooth muscle or endothelial cells.
  
  
  RESULTS
  The immunoassay of the VEGF-protein transfer showed a 10-fold greater VEGF concentration in the serum of rats carrying VEGF pumps than in the control group. In the VEGF-DNA transfer, the penes transfected with VEGF 165 vectors showed a 283-bp polymerase chain reaction product according to specific primers for human VEGF. Although statistical trends were measured in the VEGF protein-treated group, no statistically significant difference in smooth muscle or endothelial cell content was found between the control and VEGF-treated rats.
  
  
  CONCLUSIONS
  Our findings have established proof of principle for successful delivery of VEGF protein and VEGF-DNA transfer in the rat penis. This study was a prelude to attempt to manipulate genetically expression of angiogenic factors in insufficient erectile tissue as a curative therapy for ED.
authors.affiliation: Department of Urology, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Burchardt
authors.forename: Tatjana
authors.initials: T
authors.lastname: Burchardt
authors.forename: Aristotelis G
authors.initials: AG
authors.lastname: Anastasiadis
authors.forename: Ralph
authors.initials: R
authors.lastname: Buttyan
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.forename: Ahmad
authors.initials: A
authors.lastname: Shabsigh
authors.forename: Jorge
authors.initials: J
authors.lastname: Frank
authors.forename: Ridwan
authors.initials: R
authors.lastname: Shabsigh
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers; D007172:Erectile Dysfunction / Q000628:therapy*; D015316:Genetic Therapy; D008297:Male; D008845:Microinjections; D010413:Penis; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000235:genetics*
chemical_list: D004337:Drug Carriers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004247:DNA