MP45-03 AGE RELATED PENILE HEMODYNAMIC IMPAIRMENT AND FIBROSIS: POSSIBLE ROLE OF GIV-WNT SIGNALING PATHWAYS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology I1 Apr 2017MP45-03 AGE RELATED PENILE HEMODYNAMIC IMPAIRMENT AND FIBROSIS: POSSIBLE ROLE OF GIV-WNT SIGNALING PATHWAYS Tung-Chin (Mike) Hsieh, Sadhna Kanoo, Jay Parikh, Valmik Bhargava, and M. Raj Rajasekaran Tung-Chin (Mike) HsiehTung-Chin (Mike) Hsieh More articles by this author , Sadhna KanooSadhna Kanoo More articles by this author , Jay ParikhJay Parikh More articles by this author , Valmik BhargavaValmik Bhargava More articles by this author , and M. Raj RajasekaranM. Raj Rajasekaran More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1421AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pathophysiology/ molecular mechanisms of age-related penile hemodynamic impairment are unclear. Previous studies suggest age-related increase in tissue fibrosis in several organs including male genital tissues leading to impaired hemodynamics and male erectile dysfunction (ED). We tested the hypothesis that increased penile/ perineal (ischiocavernosus; ICM) muscle fibrosis during advanced aging is mediated by a novel fibrogenic cascade involving GIV/girdin and Wnt signaling pathways. A clear understanding of these molecular mechanisms involved in penile fibrosis would enable development of optimal strategies to treat ED. METHODS Young (n=3; 9 months) and old (n=6; 36 months) New Zealand White rabbits were anesthetized and penile tissue microcirculatory blood perfusion (perfusion units- PU) was measured using a novel PeriCam PSI system. Blood perfusion measurements were made before and after an intracavernosal injection of vasoactive agent- PGE1 (50 ng). Penile (corpus cavernosum) and ICM tissues were harvested and paraffin sections of these tissues were subjected to: (1) trichrome staining (marker of fibrosis) followed by image analysis for evaluation of fibrosis and (2) immunostaining for specific markers of fibrosis: 1. [beta]-catenin (central mediator of Wnt pathway) and 2. GIV/girdin. RESULTS Representative tracings of time-course of penile blood perfusion measurements in response to intracavernosal PGE1 as well as age-related penile perfusion changes in young and old rabbits are shown in figure A. Photomicrographs of showing trichrome as well as immunostaining for fibrosis markers (GIV and [beta]-catenin) are depicted in Fig B. A significant impairment in penile perfusion (Fig A) and increased fibrosis of penile/ICM tissues was observed in old rabbits (Fig B) when compared to the young animals. Immunostaining studies revealed positive labelling for both GIV and and [beta]-catenin and increased immunoreactivity in the tissues from old rabbits (Fig B). CONCLUSIONS Our findings suggest age-related increase in penile/ perineal muscle (ICM) fibrosis may contribute to increased incidence of ED in older men. Targeting GIV-Wnt pathways may be beneficial in preventing age-related ED for the aging population. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e612 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Tung-Chin (Mike) Hsieh More articles by this author Sadhna Kanoo More articles by this author Jay Parikh More articles by this author Valmik Bhargava More articles by this author M. Raj Rajasekaran More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...