Pd03-07 Characterization of Prostatic Foam Cells and Lipid Accumulation in BPH

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD03)1 May 2024PD03-07 CHARACTERIZATION OF PROSTATIC FOAM CELLS AND LIPID ACCUMULATION IN BPH Samara V. Silver, Kayah J. Tucker, Chunghwan Ro, Nehemiah Alvarez, and Petra Popovics Samara V. SilverSamara V. Silver , Kayah J. TuckerKayah J. Tucker , Chunghwan RoChunghwan Ro , Nehemiah AlvarezNehemiah Alvarez , and Petra PopovicsPetra Popovics View All Author Informationhttps://doi.org/10.1097/01.JU.0001009388.01015.e5.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH), causing deteriorating lower urinary tract symptoms (LUTS), is recognized as a disease of multiple pathologies, including nodular tissue growth, smooth muscle dysfunction, inflammation and fibrosis. We have recently identified the presence of lipid-accumulating macrophages, known as foam cells, that mainly localize in the prostate lumen in BPH specimens. This implies some form of lipid dysregulation in the prostate. However, the role of foam cells and lipid accumulation as pathological factors in BPH has not been previously investigated. Therefore, we investigated whether luminal foam cells and prostatic lipid accumulation are associated with BPH and conducted scRNA-seq on prostates from a mouse BPH model to characterize the foam cell transcriptome. METHODS: Wholemount frozen sections of donor and BPH prostates from were stained with Oil Red O and regions of glandular nodules, internodular regions in BPH and normal transition zone in donor tissues were imaged at 40x magnification. Male C57BL/6J mice were implanted with 25 mg testosterone and 2.5 mg estradiol ventral prostates were collected two weeks later. scRNA-seq was conducted on a NextSeq2000 instrument at 100 million reads/sample and results were confirmed using in situ hybridization (ISH) or immunohistochemistry (IHC). Tissue samples were analyzed using a Mantra II. Pathological Workstation and InForm software. RESULTS: In human prostates, we found significant elevation in lipid accumulation as well as an increase in lumens positive for CD68+ macrophages in BPH compared to donor transition zone. In mice, we identified five distinct macrophage clusters: MacFolr2+, MacPmepa1+, MacEar2+, MacCd209a+, and MacSpp1+. MacSpp1+ represented foam cells and were also marked by Gpnmb, Trem2, Fabp5, Ctsl and Mmp12 expression. Several cytokines and growth factors, including Tgfb1, Vegf, Cxcl16, and Ccl6, were also significantly upregulated in MacSpp1+ (confirmed via ISH and IHC). In addition, epithelial Cxcl17 expression, a known regulator of macrophage infiltration, was significantly increased (13-fold, p<0.001), suggesting its role in the luminal translocation of macrophages. CONCLUSIONS: Our results suggest that lipid accumulation is a novel pathological process in BPH and foam cells migrate to the lumen in response to Cxcl17 to secrete pathogenic factors that may promote inflammation and fibrosis in the prostate. These findings indicate that therapies targeting prostatic lipid dysregulation and macrophage infiltration may improve the treatment of BPH patients. Source of Funding: This study was supported by grants from the National Institutes of Health including K01 DK127150-01 (to P.P) and a start-up fund provided by EVMS (to P.P.) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e78 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Samara V. Silver More articles by this author Kayah J. Tucker More articles by this author Chunghwan Ro More articles by this author Nehemiah Alvarez More articles by this author Petra Popovics More articles by this author Expand All Advertisement PDF downloadLoading ...