You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD11)1 Sep 2021PD11-10 PROSTATE-SPECIFIC DELETION OF Cdh1 IN MICE MIMICS PROSTATIC PERFUSION OF BENIGN PROSTATIC HYPERPLASIA (BPH) PATIENTS Pradeep Tyagi, Laura Pascal, Lesley Foley, Robin Frederick, T. Kevin Hitchens, Anthony Kanai, Naoki Yoshimura, and Zhou Wang Pradeep TyagiPradeep Tyagi More articles by this author , Laura PascalLaura Pascal More articles by this author , Lesley FoleyLesley Foley More articles by this author , Robin FrederickRobin Frederick More articles by this author , T. Kevin HitchensT. Kevin Hitchens More articles by this author , Anthony KanaiAnthony Kanai More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Zhou WangZhou Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001986.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although BPH is an age-related comorbidity of cardiovascular disease and hypertension, the investigation into the direction of the relationship will require animal models. Recently, the downregulation of E-cadherin in hyperplastic nodules of BPH patients was mechanistically linked to the prostatic inflammation and vascular defects by the recapitulation of BPH phenotype following deletion of E-cadherin gene (Cdh1-/- ) in prostatic epithelium of adult mouse (Endocrinology 2021; 162(1) : bqaa212). Since the injected T1 shortening agent, Gadobutrol only resides in vascular and extracellular space, we enquired the effect of Cdh1-/-on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). METHODS: Tamoxifen injection at 7 weeks of age generated PSA-CreERT2/Cdh1-/- mice and then anaesthetized 21-23 weeks old Cdh1-/- and wild type controls (n=3) were injected Gadobutrol 0.1mm/kg for T1 weighted DCE-MRI of prostate in 9 axial slices with number of excitations (NEX)=1 and temporal resolution of 12s in voxel size of 0.156x0.156x0.8mm3 at small animal 7T scanner followed by Masson’s trichome staining. RESULTS: Although ventral lobes of Cdh1-/- mice were similar in size to age matched controls, the kinetic modelling of DCE-MRI (repetition TR/echo time TE - 200/5.23ms) determined that clearance of Gadobutrol was four fold slower from ventral lobe of Cdh1-/- mice with efflux rate constant Kep of 0.17±1.48 min-1 vs 0.88±0.08 min-1 in controls. The prostate permeability metric, Kep of Cdh1-/- mice is determined by the widened and elongated venules (# telangiectasia) and the higher density of collagen (blue stain) in ventro/lateral lobes on Masson's trichrome staining, which retains the Gadobutrol even 30min after injection to increase T1 contrast more than adjacent dorsal lobes and ventral lobe of control mice in high resolution post-contrast images (TR/TE 2000/20ms; NEX=4). CONCLUSIONS: The link between the vascular defects and expanded extracellular space of prostate in Cdh1-/- mice with the slower clearance of Gadobutrol implicates a bidirectional relationship between prostatic inflammation and prostatic vasculature defects that are characteristic of BPH. Findings suggest that E-cadherin downregulation could be a driving force in human BPH development and progression. Source of Funding: UPMC Hillman Pilot Funding; DK112079; CA211242 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e201-e202 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pradeep Tyagi More articles by this author Laura Pascal More articles by this author Lesley Foley More articles by this author Robin Frederick More articles by this author T. Kevin Hitchens More articles by this author Anthony Kanai More articles by this author Naoki Yoshimura More articles by this author Zhou Wang More articles by this author Expand All Advertisement Loading ...
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