Variable coding sequence protein A1 as a marker for erectile dysfunction.
OBJECTIVE
To investigate whether variable coding sequence protein A1 (Vcsa1) is down-regulated in rat models of diabetes and ageing, and to investigate the role of Vcsa1 in erectile function, as Vcsa1 is the most down-regulated gene in the corpora of a rat model of neurogenic erectile dysfunction (ED).


METHODS
Quantitative reverse-transcriptase polymerase-chain reaction was used to determine Vcsa1 expression in the corpora of rats in three models of ED, i.e. streptozotocin-induced diabetes, retired breeder (old), and neurogenic (bilaterally ligated cavernosal nerves), and in control rats. To confirm a physiological role of Vcsa1 in erectile function, we carried out gene transfer studies using a plasmid in which Vcsa1 was expressed from a cytomegalovirus promoter (pVAX-Vcsa1). This plasmid was injected intracorporally into old rats, and the effect on physiology of corporal tissue was analysed by intracorporal/blood pressure (ICP/BP) measurement and histological analysis, and compared with the effects of a positive control plasmid (pVAX-hSlo, which we previously reported to restore erectile function in diabetic and ageing rats) and a negative control plasmid (pVAX).


RESULTS
In each rat model of ED there was a significant down-regulation of the Vcsa1 transcript of at least 10-fold in corporal tissue. Remarkably, intracorporal injection with 80 microg pVAX-Vcsa1 caused priapism, as indicated by visible prolonged erection, histological appearance, and elevated resting ICP/BP. Lower doses of pVAX-Vcsa1 (5 and 25 microg) increased ICP/BP over that in untreated controls.


CONCLUSIONS
These results show that Vcsa1 has a role in erectile function and might be a molecular marker for organic ED. The role of Vcsa1 in erectile function suggests that it could represent a novel therapeutic target for treating ED.
Tong
Yuehong
Y
Department of Urology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Tar
Moses
M
Davelman
Felix
F
Christ
George
G
Melman
Arnold
A
Davies
Kelvin P
KP
D000375:Aging / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000150:complications / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology; D015536:Down-Regulation; D007172:Erectile Dysfunction / Q000175:diagnosis* / Q000209:etiology; D008026:Ligation; D008297:Male; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000378:metabolism* / Q000502:physiology
D015415:Biomarkers; D011498:Protein Precursors; D012471:Salivary Proteins and Peptides; C066861:Smr3b protein, rat