Vcsa1 acts as a marker of erectile function recovery after gene therapeutic and pharmacological interventions

J Urol. 2009 Jun;181(6):2806-15. doi: 10.1016/j.juro.2009.01.096. Epub 2009 Apr 17.

Abstract

Purpose: We identified molecular markers of erectile function, particularly those responding to erectile dysfunction treatment.

Materials and methods: Sprague-Dawley retired breeder rats were intracorporeally injected with pVAX-hSlo, pSMAA-hSlo or the control plasmid pVAX. One week later the intracorporeal pressure-to-blood pressure ratio and gene expression were determined by microarray analysis and quantitative reverse transcriptase-polymerase chain reaction. Rat corporeal cells were transfected in vitro with pVAX-hSlo, pSMAA-hSlo or pVAX and the change in gene expression was determined. We also determined whether Vcsa1 expression was changed after pharmacotherapy using tadalafil.

Results: Animals treated with vectors expressing hSlo had significantly improved erectile function compared to that in controls, accompanied by changed expression of a subset of genes. Vcsa1 was one of the genes that was most changed in expression (the third of approximately 31,000 with greater than 10-fold up-regulation). Changes in gene expression were different than those observed in corporeal cells transfected in vitro, distinguishing gene expression changes that were a direct effect of hSlo over expression. When tadalafil was administered in retired breeder rats, the Vcsa1 transcript increased 4-fold in corporeal tissue compared to that in untreated controls.

Conclusions: Our study identifies a set of genes that are changed in response to improved erectile function, rather than as a direct effect of treatment. We noted Vcsa1 may act as marker of the restoration of erectile function after gene transfer and pharmacotherapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carbolines / therapeutic use*
  • Erectile Dysfunction / drug therapy
  • Erectile Dysfunction / genetics
  • Erectile Dysfunction / therapy*
  • Gene Expression
  • Genetic Therapy*
  • Male
  • Penile Erection / physiology*
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Protein Precursors / genetics
  • Protein Precursors / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Salivary Proteins and Peptides / genetics
  • Salivary Proteins and Peptides / physiology*
  • Tadalafil

Substances

  • Carbolines
  • Phosphodiesterase Inhibitors
  • Protein Precursors
  • Salivary Proteins and Peptides
  • Smr3b protein, rat
  • Tadalafil