mp47-20 increased rho-kinase 2 and an increase of synthetic smooth muscle-specific marker expression...

e526 THE JOURNAL OF UROLOGY� Vol. 191, No. 4S, Supplement, Monday, May 19, 2014

MP47-19A POPULATION-BASED STUDY OF CIRCUMCISION AND NON-HIVSEXUALLY TRANSMITTED INFECTIONS IN A CONTEMPORARYGROUPOF AFRICAN AMERICAN MEN: THE FLINT MEN’S HEALTHSTUDY

Joshua Gonzalez*, New York, NY; Jim Hotaling, Salt Lake City, UT;Rod Dunn, Ann Arbor, MI; Natan Bar-Chama, New York, NY;Aruna Sarma, Ann Arbor, MI

INTRODUCTION AND OBJECTIVES: An estimated 19 millionnew sexually transmitted infections (STI) are reported annually in theUnited States, which cost the health care system $17 billion each year.The relationship between circumcision and STI risk remains contro-versial, despite several randomized controlled trials out of Africademonstrating that circumcision reduces the rate of HIV transmission byup to 76%. We sought to assess potential variable risk of non-HIVsexually transmitted infections among a large community-based cohortof circumcised and uncircumcised African American men.

METHODS: We performed a cross-sectional analysis of datafrom the Flint Men’s Health Study, a population-based cohort study ofAfrican American men. 817 men, ages 40-79, from Genesee County,Michigan provided information on clinical and sociodemographiccharacteristics, and sexual and reproductive health and practices.Relevant data collected included information on demographics,circumcision history, STI history, and sexual behaviors. Differences inthe distributions of these factors by circumcision and STI status wereexamined and tested using Pearson chi-squared tests. Additionally, amultivariate logistic regression examined the association betweencircumcision and STI, controlling for age, income, and number ofsexual partners.

RESULTS: Overall, 51% of men were circumcised with nearly60% of circumcisions occurring in the first year of life. Men aged 40-49(58.5%) were circumcised more than older men (55.9%, 44.1%, and44.0% of men aged 50-59, 60-69, and 70-79, respectively, p ¼ 0.0026).55% of men reported some history of STI with lower income associatedwith a higher rate of STI (p ¼ 0.015). Men with the greatest number ofsexual partners generally had the highest rates of STI (p < 0.0001).There was no significant association between circumcision status andSTI in the multivariable model.

CONCLUSIONS: After adjusting for known confounders, menin our study who were uncircumcised were not any more likely toreport a history of STI. Our data may challenge common beliefsregarding the protective nature of circumcision against STI, whichhave mostly been extrapolated from studies looking at HIV rates inprimarily non-American men. Further investigation may elucidate thecomplicated relationship between circumcision and STI and help drawlasting conclusions on the potential protective benefit of circumcisionin American males.

Source of Funding: None.

MP47-20INCREASED RHO-KINASE 2 AND AN INCREASE OF SYNTHETICSMOOTH MUSCLE-SPECIFIC MARKER EXPRESSION ISOBSERVED IN THE CORPUS CAVERNOSUM OF PATIENTS WITHSEVERE ERECTILE DYSFUNCTION.

Maarten Albersen, Leuven, Belgium; Trinity Bivalacqua*,Johanna Hannan, Baltimore, MD; Loes Linsen, Hasselt, Belgium;Emmanuel Weyne, Leuven, Belgium; Hanna Tinel, Peter Sandner,Wuppertal, Germany; Pieter Uvin, Leuven, Belgium; Koenraad VanRenterghem, Hasselt, Belgium

INTRODUCTION AND OBJECTIVES: Various animal modelsof erectile dysfunction (ED) have consistently shown upregulation ofthe RhoA/Rho associated protein kinase (ROCK) pathway, specificallyisoform ROCK2, in the corpus cavernosum (CC). In vascular diseasessuch as hypertension and atherosclerosis, a long-term increasedROCK activation and/or upregulation results in vascular wall fibrosisby inducing a phenotypical switch from contractile smooth muscle cells(SMCs) to synthetic SMCs, also termed myofibroblasts (MFs). Thisswitch in phenotype reflects a continuum, in which various phenotyp-ical states are reflected by the expression of a distinct set of markers.Alpha-SMC actin (aSMA) is expressed in both contractile SMCs aswell as in MFs. SMC heavy chain kinase (MYH11)is almost exclusivelyexpressed in contractile SMCs, and is not expressed in MFs. Weaimed to see whether phenotypical changes are occurring in thehuman CC SMCs by examining expression of ROCK mRNA andevaluating the regulation of genes involved in the phenotypical switchof SMCs.

METHODS: Specimen of human CC were harvested fromconsenting patients undergoing penile prosthesis implantation (n¼14patients) and potent control subjects (n¼5 healthy controls, needle bi-opsy). Tissues of patients were compared to those of healthy controlsfor the expression of mRNA coding for ROCK1, ROCK2, MYH11 andaSMA by qPCR and normalized to the expression of beta-actin. ROCKand aSMA proteins were further localized using immunofluorescence.Statistical analysis was performed using Student’s t-test or Man-neWhitney test, depending on normality of data. Data are reportedas mean�SEM.

RESULTS: aSMA, was expressed more in CC from ED vscontrol men (relative expression 504243�15265 vs 385483�25456P<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) wassignificantly upregulated in ED patients. ROCK protein colocalizedwith aSMA, confirming the presence of this kinase in SMCsand MFs.

CONCLUSIONS: We provide evidence of a dysregulation be-tween aSMA and MYH11 expression in human erectile tissue. Adecrease of MYH11 expression is indicative of a loss of SMC con-tractile phenotype. As ROCK2 was upregulated, we postulate thatchronic ROCK inhibition may be a future pharmacological target inhumans for preventing ED by interfering with smooth muscle pheno-type transition.

Source of Funding: none