Cavernous angionenesis as a novel therapeutic strategy for erectile dysfunction

초록

Despite oral phosphodiesterase type 5 inhibitors, including sildenafil citrate, are well utilized as first-line therapy for the majority of erectile dysfunction (ED) patients, there is a need for better treatment modality in those with diabetes, severe vascular dysfunction, those who had pelvic surgery, those who show significant cardiovascular side effects or those who are not flexible to the treatment with on-demand medicine. We have started on a course of study to develop local terapeutics using angiogenic factors in the field of ED. Angiogenic factor gene was applied in thes study based on the finding that cavernous angiopoietin-1 and their down stream signal molecules are downregulated in ED with gypercholesterolemia. We found that combined local delivery of both angiopoietin-1 and VEGF165 genes in hypercholesterolemic rats significantly increases cavernous endothelial contents, eNOS phosphorylation and cGMP expression, which results in full recovery of erectile function. Recently, we had an experiment to evaluate the effect of cartilage oligomeric matrix protein (COMP) - antiopoietin-1, a variant of angiopoietin-1 and much more potent than that, in penile erection. A single injection of adenoviral COMP-Ang1 gene or two successive injections of COMP-Ang1 protein significantly increased cavernous angiogenesis and resultant, long-lasting recovery of erectile function. Therefore, it appears that the local application of angiopoietin-1 based gene or protein therapy for ED represents and exciting new field.