Designed angiopoietin-1 variant, COMP-angiopoietin-1, rescues erectile function through enhanced cavernous angiogenesis and blood flow in a hypercholesterolemic mouse

초록

Despite the advent of oral phosphodiesterase-5 inhibitors, curative treatment for erectile dysfunction (ED) remains unavailable. Recently, the link between ED and cardiovascular disease was unveiled and the main etiology of ED was found to be vasculogenic. Therefore, neovascularization is a promising strategy for curing ED. Angiopoietin-1 (Ang1) is an angiogenic growth fctor the promotes the generation of stable and functional vasculature. Here, we demonstrate that local delivery of the soluble, stable, and potent Ang1 variant, adenoviral COMP-Ang 1 gene or COMP-Ang1 protein, into the penises of hypercholesterolemic mice increases cavernous angiogenesis, endothelial nitric oxide synthase (eNOS) phosphorylation, and cGMP expression, resulting in full recovery of erectile function and cavernous blood flow up to 8 weeks after treatment. COMP-Ang1-induced promotion of cavernous angiogenesis and erectile function was abolished in Nos3-/- mice and in the presence of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). These findings support the concept of angiogenic factor therapy as curative therapy for ED. Local therpy with COMP-Ang1, especially in protein form, is highly promising as a definitive treatment modality for vascular disese-induced ED.