title: Sac-1004, a Pseudo-Sugar Derivative of Cholesterol, Restores Erectile Function through Reconstruction of Nonleaky and Functional Cavernous Angiogenesis in the Streptozotocin Induced Diabetic Mouse.
abstract: We examined whether and how Sac-1004, a vascular leakage blocker, would restore erectile function in an animal model of diabetic erectile dysfunction.
  
  
  
  Eight-week-old C57BL/6J mice were used. Diabetes was induced by intraperitoneal injection of streptozotocin. Eight weeks after diabetes induction the animals were divided into 6 groups, including controls, diabetic mice that received repeat intracavernous injections of phosphate buffered saline (20 μl) on days -3 and 0, and diabetic mice that received repeat intracavernous injections of Sac-1004 on days -3 and 0 (1, 2, 5 and 10 μg, respectively, in 20 μl phosphate buffered saline). One week after injection erectile function was measured by cavernous nerve stimulation. The penis was then harvested for histological examinations and Western blot analysis.
  
  
  
  Local delivery of Sac-1004 in the corpus cavernosum restored erectile function in diabetic mice. The highest erectile response was noted at a dose of 5 μg with a response comparable to that in the control group. Sac-1004 significantly increased cavernous endothelial and smooth muscle contents, and induced endothelial nitric oxide synthase phosphorylation (Ser1177). Sac-1004 decreased extravasation of oxidized low density lipoprotein 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 inhibiting angiopoietin-1-Tie2 signaling with soluble Tie2 antibody.
  
  
  
  With the effects of angiogenesis and antipermeability Sac-1004 reestablishes structural and functional cavernous sinusoids. This is highly promising for future treatment of erectile dysfunction from vascular causes.
authors.affiliation: National Research Center for Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Dulguun
authors.initials: D
authors.lastname: Batbold
authors.affiliation: National Research Center for Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Kang-Moon
authors.initials: KM
authors.lastname: Song
authors.affiliation: National Research Center for Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Jin-Mi
authors.initials: JM
authors.lastname: Park
authors.affiliation: National Research Center for Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Soo-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: National Research Center for Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Tack
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Urology, Sungkyunkwan University School of Medicine, Samsung Changwon Hospital, Changwon, Republic of Korea.
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Ryu
authors.affiliation: Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Young-Ger
authors.initials: YG
authors.lastname: Suh
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
authors.affiliation: National Research Center for Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea; Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, Republic of Korea. Electronic address: rjk0929@inha.ac.kr.
authors.forename: Ji-Kan
authors.initials: JK
authors.lastname: Ryu
authors.affiliation: National Research Center for Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea. Electronic address: jksuh@inha.ac.kr.
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D013311:Streptozocin; D016896:Treatment Outcome
chemical_list: D043925:Angiogenesis Inducing Agents; C583002:CU06-1004; D012503:Saponins; D013311:Streptozocin
keywords: Sac-1004; angiogenesis inducing agents; diabetes mellitus; erectile dysfunction; penis