Vcsa1 acts as a marker of erectile function recovery after gene therapeutic and pharmacological interventions.
OBJECTIVE
We identified molecular markers of erectile function, particularly those responding to erectile dysfunction treatment.


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.
Department of Urology and Institute of Smooth Muscle Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Giulia
G
Calenda
Yuehong
Y
Tong
Moses
M
Tar
Daniel
D
Lowe
Joseph
J
Siragusa
Arnold
A
Melman
Kelvin P
KP
Davies
D000818:Animals; D002243:Carbolines / Q000627:therapeutic use*; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy; D008297:Male; D010410:Penile Erection / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000502:physiology*; D000068581:Tadalafil
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D011498:Protein Precursors; D012471:Salivary Proteins and Peptides; C066861:Smr3b protein, rat; D000068581:Tadalafil