Combined angiopoietin-1 and vascular endothelial growth factor gene transfer restores cavernous angiogenesis and erectile function in a rat model of hypercholesterolemia

Ji Kan Ryu, Chung Hyun Cho, Hwa Yean Shin, Sun U. Song, Seung Min Oh, Minhyung Lee, Shuguang Piao, Jee Young Han, In Hoo Kim, Gou Young Koh, Jun Kyu Suh

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Hypercholesterolemia-related endothelial cell dysfunction and decreased endothelium-derived nitric oxide formation may account for impaired angiogenesis and subsequent erectile dysfunction. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. We hypothesized that combined adenovirus-delivered human Ang1 (ad-Ang1) and VEGF165 (ad-VEGF165) gene transfer might promote angiogenesis cooperatively in a rat model of hypercholesterolemic erectile dysfunction and result in a recovery of erectile function. Ad-Ang1 and ad-VEGF165 were injected either alone or in combination into the corpus cavernosum of the penis. Combined gene transfer of both ad-Ang1 and ad-VEGF165 significantly increased cavernous angiogenesis, eNOS phosphorylation, and cGMP expression compared with that in the groups treated with either therapy alone. Erectile function, as evaluated by electrical stimulation of the cavernous nerve 2 and 8 weeks after treatment, was completely restored in the combined treatment group, whereas intracavernous injection of either ad-Ang1 or ad-VEGF165 alone elicited partial improvement. The results indicate that combined application of angiogenic factors may enhance cavernous angiogenesis cooperatively by reinforcing the endothelium both structurally and functionally, which results in an additive effect on erectile function in hypercholesterolemic rats.

Original languageEnglish
Pages (from-to)705-715
Number of pages11
JournalMolecular Therapy
Volume13
Issue number4
DOIs
StatePublished - 2006 Apr 1

Keywords

  • Adenoviral vector
  • Angiogenesis
  • Angiopoietin-1
  • Erectile dysfunction
  • Gene therapy
  • Hyperlipidemia
  • Vascular endothelial growth factor

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