Downregulation of angiogenic factors and their downstream target molecules affects the deterioration of erectile function in a rat model of hypercholesterolemia.
OBJECTIVE
To evaluate how the expression of angiogenic factors and their downstream target molecules, which are potentially involved in penile homeostasis, is related to erectile dysfunction in a rat model of hypercholesterolemia.


METHODS
Fifty-six 2-month-old male Sprague-Dawley rats were included in this study. The control animals (n = 28) were fed a normal diet, and the experimental animals (n = 28) were fed a diet containing 4% cholesterol and 1% cholic acid for 3 months. Erectile function was evaluated by cavernous nerve electrical stimulation, and cavernous tissue was harvested for histologic examination (n = 12, respectively). Cavernous tissue specimens from the remaining rats were used for reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, or cyclic guanosine monophosphate (cGMP) measurement.


RESULTS
The ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the hypercholesterolemic rats than in the controls (P <0.01). Analysis by RT-PCR and Western blot showed significantly lower gene expression of vascular endothelial growth factor (VEGF), angiopoietin-1, and angiopoietin-2 and significantly lower protein expression of VEGF, angiopoietin-1, angiopoietin-2, the ratio of phospho-Akt to Akt, and phospho-endothelial nitric oxide synthase (eNOS) to eNOS in hypercholesterolemic rats than in controls. Cavernous tissue cGMP concentrations and endothelial area were also significantly lower in hypercholesterolemic rats than in controls (P <0.01).


CONCLUSIONS
Downregulation of the expression of the angiogenic factors and their downstream signal molecules, and decreased endothelial content in the corpus cavernosum of hypercholesterolemic rats might play important roles in the deterioration of erectile function.
Ryu
Ji-Kan
JK
Department of Urology, Clinical Research Center, Inha University School of Medicine, Jung-Gu, Incheon, Republic of Korea.
Shin
Hwa-Yean
HY
Song
Sun U
SU
Oh
Seung-Min
SM
Piao
Shuguang
S
Han
Jee-Young
JY
Park
Kwang-Won
KW
Suh
Jun-Kyu
JK
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D007172:Erectile Dysfunction / Q000209:etiology*; D006937:Hypercholesterolemia / Q000150:complications* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D043925:Angiogenesis Inducing Agents