title: Systemic atherosclerosis causes detrusor overactivity: functional and morphological changes in hyperlipoproteinemic apoE-/-LDLR-/- mice.
abstract: OBJECTIVE
  The prevalence of systemic atherosclerosis and overactive bladder/detrusor overactivity increases almost simultaneously with age but an association between these diseases has not yet been proved. We evaluated changes in bladder function and morphology, including vascularization, in apoE(-/-)LDLR(-/-) double knockout mice with systemic atherosclerosis but without central nervous system involvement.
  
  
  METHODS
  Cystometry was performed in awake, freely moving 60-week-old apoE(-/-)LDLR(-/-) mice and C57BL/6N controls. The mice were sacrificed and perfused with Microfil® contrast medium. The bladder was excised, dissected and scanned by nano-computerized tomography, including 3-dimensional reconstruction. Samples then underwent histomorphological analysis.
  
  
  RESULTS
  In apoE(-/-)LDLR(-/-) mice cystometry revealed a significant decrease in the peak-peak interval, micturition interval, functional bladder capacity and micturition volume. However, maximum bladder pressure increased. Nano-computerized tomography revealed a significant reduction in bladder wall thickness, segment volume, vascular volume and the vascular volume fraction. Histomorphologically bladder specimens showed a thickened media of intramural vessels, activated endothelial cells and intramural inflammatory cells.
  
  
  CONCLUSIONS
  To our knowledge this study presents a new in vivo mouse model of nonneurogenic detrusor overactivity caused by systemic atherosclerosis. Decreased bladder wall vascularization seems to be a major factor for detrusor overactivity onset. Capillaries are rarified with reduced lumina due to thickened media. Activated endothelial cells and the infiltration of inflammatory cells in apoE(-/-)LDLR(-/-) mice underlines once more that atherosclerosis is an inflammatory process that may also be relevant to the onset of detrusor overactivity.
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Justus-Liebig University Giessen, Giessen, Germany. Electronic address: Th.B@gmx.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bschleipfer
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Dannenmaier
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Illig
authors.affiliation: Institute for Pathology, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Kreisel
authors.affiliation: Institute for Pathology, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenlöhner
authors.affiliation: Department of Diagnostic and Interventional Radiology, BG Trauma Hospital Frankfurt/Main, Frankfurt/Main, Germany.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Langheinrich
authors.affiliation: Department of Diagnostic Radiology, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Gabriele A
authors.initials: GA
authors.lastname: Krombach
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weidner
authors.affiliation: Department of Diagnostic Radiology, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Marian
authors.initials: M
authors.lastname: Kampschulte
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications* / Q000235:genetics; D005260:Female; D006951:Hyperlipoproteinemias / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics; D001743:Urinary Bladder / Q000473:pathology* / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D001057:Apolipoproteins E; D011973:Receptors, LDL
keywords: animal; atherosclerosis; emission-computed; inflammation; models; overactive; tomography; urinary bladder