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Ryu, Ji-Kan,Tumurbaatar, Munkhbayar,Jin, Hai-Rong,Kim, Woo Jean,Kwon, Mi-Hye,Piao, Shuguang,Choi, Min Ji,Yin, Guo Nan,Song, Kang-Moon,Kang, Yong-Jin,Koh, Young Jun,Koh, Gou Young,Suh, Jun-Kyu Blackwell Pub 2012 JOURNAL OF SEXUAL MEDICINE Vol.9 No.12
<P>Men with diabetic erectile dysfunction (ED) often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors.</P>
Ryu, Ji-Kan,Zhang, Lu Wei,Jin, Hai-Rong,Piao, Shuguang,Choi, Min Ji,Tuvshintur, Buyankhuu,Tumurbaatar, Munkhbayar,Shin, Sun Hwa,Han, Jee-Young,Kim, Woo Jean,Suh, Jun-Kyu Blackwell Pub 2009 The journal of sexual medicine Vol.6 No.7
<P>Endothelial cell-to-cell junctions are crucial for vascular formation, networking, and remodeling of blood vessels as well as for inducing and integrating intracellular signals.</P>
Jin, Hai-Rong,Kim, Woo Jean,Song, Jae Sook,Piao, Shuguang,Choi, Min Ji,Tumurbaatar, Munkhbayar,Shin, Sun Hwa,Yin, Guo Nan,Koh, Gou Young,Ryu, Ji-Kan,Suh, Jun-Kyu American Diabetes Association 2011 Diabetes Vol.60 No.3
<P><B>OBJECTIVE</B></P><P>Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test.</P><P><B>RESULTS</B></P><P>Local delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47<SUP>phox</SUP> and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, <I>N</I>-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin.</P><P><B>CONCLUSIONS</B></P><P>These findings support the concept of cavernous endothelial regeneration by use of the recombinant Ang1 protein as a curative therapy for diabetic erectile dysfunction.</P>