title: Derangements in endothelial cell-to-cell junctions involved in the pathogenesis of hypercholesterolemia-induced erectile dysfunction.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We investigated the differential expression and distribution of endothelial cell-to-cell junction proteins in the penis of mice with hypercholesterolemia-induced erectile dysfunction.
  
  
  METHODS
  Two-month-old C57BL/6J mice were fed a diet containing 4% cholesterol and 1% cholic acid, and age-matched control animals were fed a normal diet, for 3 months. We performed dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) (Seegene, Seoul, Korea) to screen the differential gene expression of 21 endothelial cell-to-cell junctions.
  
  
  METHODS
  At 5 months, erectile function was measured by electrical stimulation of the cavernous nerve, and the penis was harvested and stained with antibody to claudin-5, vascular endothelial (VE)-cadherin, and platelet/endothelial cell adhesion molecule (PECAM)-1 (N = 8 per group). Cavernous specimens from a separate group of animals were used for claudin-5, VE-cadherin, and PECAM-1 reverse transcriptase-PCR and Western blot analysis.
  
  
  RESULTS
  Erectile function was significantly lower in hypercholesterolemic mice than in controls. DPO-based multiplex PCR revealed a profound decrease in the gene expression of endothelium-specific cell-to-cell junction proteins, including claudin-5, VE-cadherin, and PECAM-1, in hypercholesterolemic mice compared with that in controls. The expression of claudin-5, VE-cadherin, and PECAM-1 protein evaluated by Western blot or immunohistochemistry was significantly lower in hypercholesterolemic mice than in controls. These endothelial cell-to-cell junction proteins were more sparsely distributed in the endothelium of cavernous sinusoids than in the endothelium of cavernous artery and dorsal blood vessels.
  
  
  CONCLUSIONS
  Down-regulation of the endothelial cell-to-cell junctions and decreased endothelial content in the corpus cavernosum might play a major role in the deterioration of erectile function in hypercholesterolemic mice.
authors.affiliation: Department of Urology and National Research Laboratory of Regenerative Sexual Medicine, Inha University School of Medicine, 7-206 3rd Street, Shinheung-Dong, Jung-Gu, Incheon, Korea.
authors.forename: Ji-Kan
authors.initials: JK
authors.lastname: Ryu
authors.forename: Lu Wei
authors.initials: LW
authors.lastname: Zhang
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Jin
authors.forename: Shuguang
authors.initials: S
authors.lastname: Piao
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Choi
authors.forename: Buyankhuu
authors.initials: B
authors.lastname: Tuvshintur
authors.forename: Munkhbayar
authors.initials: M
authors.lastname: Tumurbaatar
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Shin
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Han
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Kim
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins; D062507:Claudin-5; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D015870:Gene Expression; D006937:Hypercholesterolemia / Q000150:complications*; D018783:Impotence, Vasculogenic / Q000209:etiology* / Q000235:genetics; D007365:Intercellular Junctions / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III; D010413:Penis / Q000187:drug effects / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D062507:Claudin-5; D008565:Membrane Proteins; D052250:Nitric Oxide Synthase Type III; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000099152:Cadherin 5; C107466:CLDN5 protein, human; C496314:NOS3 protein, human