Combined angiopoietin-1 and vascular endothelial growth factor gene transfer restores cavernous angiogenesis and erectile function in a rat model of hypercholesterolemia.
Hypercholesterolemia-related endothelial cell dysfunction and decreased endothelium-derived nitric oxide formation may account for impaired angiogenesis and subsequent erectile dysfunction. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. We hypothesized that combined adenovirus-delivered human Ang1 (ad-Ang1) and VEGF165 (ad-VEGF165) gene transfer might promote angiogenesis cooperatively in a rat model of hypercholesterolemic erectile dysfunction and result in a recovery of erectile function. Ad-Ang1 and ad-VEGF165 were injected either alone or in combination into the corpus cavernosum of the penis. Combined gene transfer of both ad-Ang1 and ad-VEGF165 significantly increased cavernous angiogenesis, eNOS phosphorylation, and cGMP expression compared with that in the groups treated with either therapy alone. Erectile function, as evaluated by electrical stimulation of the cavernous nerve 2 and 8 weeks after treatment, was completely restored in the combined treatment group, whereas intracavernous injection of either ad-Ang1 or ad-VEGF165 alone elicited partial improvement. The results indicate that combined application of angiogenic factors may enhance cavernous angiogenesis cooperatively by reinforcing the endothelium both structurally and functionally, which results in an additive effect on erectile function in hypercholesterolemic rats.
Ryu
Ji-Kan
JK
Department of Urology, Inha University School of Medicine, Incheon 400-711, Republic of Korea.
Cho
Chung-Hyun
CH
Shin
Hwa-Yean
HY
Song
Sun U
SU
Oh
Seung-Min
SM
Lee
Minhyung
M
Piao
Shuguang
S
Han
Jee-Young
JY
Kim
In-Hoo
IH
Koh
Gou Young
GY
Suh
Jun-Kyu
JK
D000256:Adenoviridae / Q000235:genetics; D042683:Angiopoietin-1 / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000188:drug therapy; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use
D042683:Angiopoietin-1; D042461:Vascular Endothelial Growth Factor A