title: Erectile dysfunction precedes other systemic vascular diseases due to incompetent cavernous endothelial cell-cell junctions.
abstract: OBJECTIVE
  Erectile dysfunction is often a harbinger of cardiovascular disease. We sought to gain mechanistic insight at the cellular and molecular levels into why erectile dysfunction precedes the clinical consequences of cardiovascular disease.
  
  
  METHODS
  Diabetes was induced by intraperitoneal streptozotocin injection in 8-week-old C57BL/6J mice. At 8 weeks after diabetes induction, we determined the expression of endothelial cell-cell junction proteins and vascular endothelial permeability in the penis, heart and hind limb by systemic injection of various vascular space markers (350 Da to 2,000 kDa) or by immunohistochemical staining with antibody to oxidized low density lipoprotein. We also investigated the effect of recombinant Ang1 protein on cavernous endothelial permeability.
  
  
  RESULTS
  Alterations in the integrity of the endothelial cell-cell junction, including a decrease in endothelial cell-cell junction proteins and an increase in vascular permeability to fluorescent tracers or oxidized low density lipoprotein, were prominent in the cavernous tissue of diabetic mice. In contrast, no significant changes in endothelial cell-cell junction proteins or vascular permeability were noted in heart or hind limb tissue according to the diabetic condition. Intracavernous injection of Ang1 protein, an anti-permeability factor, significantly decreased cavernous endothelial permeability to oxidized low density lipoprotein by restoring endothelial cell-cell junction proteins in diabetic mice.
  
  
  CONCLUSIONS
  The incompetent cavernous endothelial cell-cell junction in the diabetic condition provides an important clue to why erectile dysfunction is highly prevalent and often precedes other systemic vascular diseases.
authors: National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea.
authors: Ji-Kan
authors: JK
authors: Ryu
authors: Hai-Rong
authors: HR
authors: Jin
authors: Guo Nan
authors: GN
authors: Yin
authors: Mi-Hye
authors: MH
authors: Kwon
authors: Kang-Moon
authors: KM
authors: Song
authors: Min Ji
authors: MJ
authors: Choi
authors: Jin-Mi
authors: JM
authors: Park
authors: Nando Dulal
authors: ND
authors: Das
authors: Ki-Dong
authors: KD
authors: Kwon
authors: Dulguun
authors: D
authors: Batbold
authors: Tack
authors: T
authors: Lee
authors: Zhen Li
authors: ZL
authors: Gao
authors: Kyu-Won
authors: KW
authors: Kim
authors: Woo Jean
authors: WJ
authors: Kim
authors: Jun-Kyu
authors: JK
authors: Suh
mesh_terms: D000704:Analysis of Variance; D042683:Angiopoietin-1 / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D003326:Coronary Circulation; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D007172:Erectile Dysfunction / Q000503:physiopathology*; D006614:Hindlimb / Q000098:blood supply; D007365:Intercellular Junctions / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010413:Penis / Q000098:blood supply; D018709:Statistics, Nonparametric
chemical_list: D042683:Angiopoietin-1
keywords: Ang1; CVD; EC; ED; HUVEC; ICP; LDL; MCEC; NO; PECAM-1; VE; ZO-1; angiopoietin-1; cardiovascular disease; cardiovascular diseases; diabetes mellitus; endothelial cell-cell; erectile dysfunction; human umbilical vein endothelial cell; intracavernous pressure; intracellular junctions; low density lipoprotein; mouse cavernous endothelial cell; nitric oxide; penis; platelet/endothelial cell adhesion molecule-1; vascular endothelial; zonular occludens-1