Vcsa1Acts as a Marker of Erectile Function Recovery After Gene Therapeutic and Pharmacological Interventions

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.

Peptides in Seminal Fluid and Their Role in Infertility: A Potential Role for Opiorphin Inhibition of Neutral Endopeptidase Activity as a Clinically Relevant Modulator of Sperm Motility: A Review

“…19 Several recent reports have demonstrated that there is an endogenous NEP/APN inhibitor peptide called opiorphin in seminal plasma. [23][24][25][26][27] In rats, sialorphin, the opiorphin homologue, is primarily expressed in the corpus cavernosum, prostate, and the submandibular gland and its expression is under androgenic regulation. 23,28 The mean concentration of opiorphin in human semen is 12.9 + 1.8 ng/mL (mean + standard error of the mean).…”

Whole genome microarray of the major pelvic ganglion after cavernous nerve injury: new insights into molecular profile changes after nerve injury

“…The effects of CN injury on global gene expression in the MPG were explored by whole genome microarray expression analysis at both the 48‐h and 14‐day timepoints after CN crush injury. As previously described [22,23], we conducted a preliminary analysis showing that, 48 h after CN injury, 325 genes were differentially expressed ( P < 0.001, B > 4) compared to sham MPG. At 14 days after CN crush injury, 114 genes were differentially expressed.…”

Silencing MaxiK Activity in Corporal Smooth Muscle Cells Initiates Compensatory Mechanisms to Maintain Calcium Homeostasis

“…We performed a total of seven micro‐array analyses using four chips for the silenced, and three chips for the control human corporal cells. Gene expression in the silenced cells was compared with controls using AffylmGUI software, available from http://www.bioconductor.org as previously described [23,30]. Data have been submitted to the NCBI Gene Expression Omnibus repository and can be accessed following the link http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jzgpruaqyyiogbc&acc=GSE19672.…”