Arteriogenic erectile dysfunction alters protein expression within the cavernosal tissue in an animal model.
BACKGROUND
Erectile dysfunction (ED) is a highly prevalent and often untreated condition. It may be a marker of underlying chronic illness and negatively impacts quality of life. Penile arterial insufficiency, frequently found in association with hypertension, dyslipidemia, diabetes mellitus, pelvic irradiation, trauma, and smoking, is the most common cause of ED.


OBJECTIVE
This study was designed to measure the effect of penile hypoperfusion-induced alteration and injury on erectile tissue at the cellular and protein level.


METHODS
Eighteen 4-month-old male Sprague Dawley rats were placed into three groups (n = 6): sham surgery, unilateral internal iliac artery ligation (UIIAL), and bilateral internal iliac artery ligation (BIIAL).


METHODS
Erectile function was assessed 4 weeks following arterial ligation surgery as measured by a rise in intracavernosal pressure induced by cavernosal nerve stimulation. Penile tissue alterations were characterized by immunohistochemistry, protein content measured by western blot, and "global" protein expression profile carried out by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip technology.


RESULTS
Significantly lower intracavernous pressures were demonstrated in animals subjected to UIIAL surgery, which correlated to the extent of artery ligation. The intensity and quantity of immunohistochemical staining for neuronal nitric oxide synthase, endothelial cell integrity, smooth muscle cell alpha-actin, and vascular endothelial growth factor (VEGF) receptor flk1 were decreased in the BIIAL group compared to sham controls. SELDI-TOF-MS analysis revealed changes in molecular expression of a approximately 6,560 Da protein relative to a 7,720 Da protein (peak ratio = 1.34 +/- 0.3, BIIAL; 0.36 +/- 0.1 controls, P < 0.05).


CONCLUSIONS
In this report, an animal model of vascular penile insufficiency demonstrates altered protein expression associated with cavernosal tissue injury and reduced erectile function. Although the clinical significance of these observations is currently undefined, this model may allow greater insight into the complex biologic changes associated with arteriogenic ED in man.
De Young
Ling
L
Division of Urology, Department of Surgery, The University of Western Ontario, London, Ontario, Canada.
Bella
Anthony
A
Howard
Jeffrey
J
Brock
Gerald
G
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004558:Electric Stimulation; D042783:Endothelial Cells / Q000378:metabolism; D007172:Erectile Dysfunction / Q000378:metabolism*; D007083:Iliac Artery / Q000293:injuries; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010413:Penis / Q000098:blood supply* / Q000294:innervation / Q000378:metabolism*; D011312:Pressure; D040081:Protein Array Analysis; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000199:Actins; D019001:Nitric Oxide Synthase; D011506:Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2; C498862:Acta2 protein, rat