Sac-1004, a Pseudo-Sugar Derivative of Cholesterol, Restores Erectile Function through Reconstruction of Non-Leaky and Functional Cavernous Angiogenesis in the Streptozotocin-Induced Diabetic Mouse

To examine whether and how Sac-1004, a vascular-leakage blocker, restores erectile function in an animal models of diabetic erectile dysfunction.

Eight-week-old C57BL/6J mice were used and diabetes was induced by intraperitoneal injection of streptozotocin.

At 8 weeks after induction of diabetes, the animals were divided into 6 groups: controls; diabetic mice receiving repeated intracavernous injections of PBS (days -3 and 0; 20 μL); and diabetic mice receiving repeated intracavernous injections of Sac-1004 (days -3 and 0; 1 μg, 2 μg, 5 μg, and 10 μg in 20 μL of PBS, respectively). One week after injection, erectile function was measured by cavernous nerve stimulation. The penis was then harvested for histologic examinations and Western blot analysis.

Local delivery of Sac-1004 into the corpus cavernosum restored erectile function in diabetic mice. The highest erectile response was noted at a dose of 5 μg, for which the response was comparable to that in the control group. Sac-1004 significantly increased cavernous endothelial and smooth muscle contents and induced eNOS phosphorylation (Ser1177). Sac-1004 decreased extravasation of oxidized-LDL by restoring endothelial cell-cell junction proteins and pericyte content. Sac-1004 also promoted tube formation in primary cultured mouse cavernous endothelial cells in vitro. Sac-1004-mediated cavernous angiogenesis and erectile function recovery was abolished by inhibition of angiopoietin-1-Tie2 signaling with soluble Tie2 antibody.

Sac-1004 with the effect of angiogenesis and anti-permeability re-establishes structural and functional cavernous sinusoids, which will be a highly promising for future treatment of erectile dysfunction from vascular causes.

The Journal of urology. 2016 Jan 23 [Epub ahead of print]

Dulguun Batbold, Kang-Moon Song, Jin-Mi Park, Soo-Hwan Park, Tack Lee, Dong-Soo Ryu, Young-Ger Suh, Young-Guen Kwon, Ji-Kan Ryu, Jun-Kyu Suh

National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea. , National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea. , National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea. , National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea. , National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea. , Department of Urology, Sungkyunkwan University School of Medicine, Samsung Changwon Hospital, Changwon 630-522, Korea. , Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul 151-742, Korea. , Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea. , National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea; Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon 400-711, Korea. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea.  

PubMed

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