MP47-20 INCREASED RHO-KINASE 2 AND AN INCREASE OF SYNTHETIC SMOOTH MUSCLE-SPECIFIC MARKER EXPRESSION IS OBSERVED IN THE CORPUS CAVERNOSUM OF PATIENTS WITH SEVERE ERECTILE DYSFUNCTION.

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2014MP47-20 INCREASED RHO-KINASE 2 AND AN INCREASE OF SYNTHETIC SMOOTH MUSCLE-SPECIFIC MARKER EXPRESSION IS OBSERVED IN THE CORPUS CAVERNOSUM OF PATIENTS WITH SEVERE ERECTILE DYSFUNCTION. Maarten Albersen, Trinity Bivalacqua, Johanna Hannan, Loes Linsen, Emmanuel Weyne, Hanna Tinel, Peter Sandner, Pieter Uvin, and Koenraad Van Renterghem Maarten AlbersenMaarten Albersen More articles by this author , Trinity BivalacquaTrinity Bivalacqua More articles by this author , Johanna HannanJohanna Hannan More articles by this author , Loes LinsenLoes Linsen More articles by this author , Emmanuel WeyneEmmanuel Weyne More articles by this author , Hanna TinelHanna Tinel More articles by this author , Peter SandnerPeter Sandner More articles by this author , Pieter UvinPieter Uvin More articles by this author , and Koenraad Van RenterghemKoenraad Van Renterghem More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1473AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Various animal models of erectile dysfunction (ED) have consistently shown upregulation of the RhoA/Rho associated protein kinase (ROCK) pathway, specifically isoform ROCK2, in the corpus cavernosum (CC). In vascular diseases such as hypertension and atherosclerosis, a long-term increased ROCK activation and/or upregulation results in vascular wall fibrosis by inducing a phenotypical switch from contractile smooth muscle cells (SMCs) to synthetic SMCs, also termed myofibroblasts (MFs). This switch in phenotype reflects a continuum, in which various phenotypical states are reflected by the expression of a distinct set of markers. Alpha-SMC actin (aSMA) is expressed in both contractile SMCs as well as in MFs. SMC heavy chain kinase (MYH11)is almost exclusively expressed in contractile SMCs, and is not expressed in MFs. We aimed to see whether phenotypical changes are occurring in the human CC SMCs by examining expression of ROCK mRNA and evaluating the regulation of genes involved in the phenotypical switch of SMCs. Methods Specimen of human CC were harvested from consenting patients undergoing penile prosthesis implantation (n=14 patients) and potent control subjects (n=5 healthy controls, needle biopsy). Tissues of patients were compared to those of healthy controls for the expression of mRNA coding for ROCK1, ROCK2, MYH11 and aSMA by qPCR and normalized to the expression of beta-actin. ROCK and aSMA proteins were further localized using immunofluorescence. Statistical analysis was performed using Student’s t-test or Mann–Whitney test, depending on normality of data. Data are reported as mean±SEM. Results aSMA, was expressed more in CC from ED vs control men (relative expression 504243±15265 vs 385483±25456 P<0.05), while MYH11 was downregulated 6-fold in ED patients (26916±5131 vs 156658±14333 P<0.05). ROCK1 was unchanged (P>0.05), while ROCK2 (7570±3013 vs 2924±432 P<0.05) was significantly upregulated in ED patients. ROCK protein colocalized with aSMA, confirming the presence of this kinase in SMCs and MFs. Conclusions We provide evidence of a dysregulation between aSMA and MYH11 expression in human erectile tissue. A decrease of MYH11 expression is indicative of a loss of SMC contractile phenotype. As ROCK2 was upregulated, we postulate that chronic ROCK inhibition may be a future pharmacological target in humans for preventing ED by interfering with smooth muscle phenotype transition. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e526 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Maarten Albersen More articles by this author Trinity Bivalacqua More articles by this author Johanna Hannan More articles by this author Loes Linsen More articles by this author Emmanuel Weyne More articles by this author Hanna Tinel More articles by this author Peter Sandner More articles by this author Pieter Uvin More articles by this author Koenraad Van Renterghem More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...