(219) Vimentin and Collagen Type 1/Type 3 Ratio as Potential Peyronie’s Disease Plaque Markers of Collagenase Efficacy

Introduction Intraplaque injection of collagenase is a therapeutic approach for treating Peyronie’s disease (PD) that may represent an alternative to surgery in some patients. However, the efficacy of collagenase injection is rather variable among patients. Objective We aimed to evaluate different tissue markers related to fibrotic process in PD plaques as potential indicators of the response to collagenase Methods After obtaining ethics committee approvals, PD plaques were obtained from 15 adult patients (54.5±2.0 years-old) undergoing penile surgery involving plaque excision for the treatment of PD and giving their written informed consent. Tissues of tunica albuginea (TA) from 10 deceased organ donors (44.5±5.3 years-old, n.s.) without notice of PD were used as controls. Tissues obtained in surgical procedures were immediately immersed in ice cold M-400 medium and transported to laboratory in the next 24 hours under refrigerated conditions. Plaque specimens were divided into portions. One piece was frozen in liquid nitrogen and stored at -80°C until used for determining protein expression by immunoblotting. Tumor growth factor-β1 (TGFβ1) was assessed by ELISA. Control TA tissues were processed in the same way. For evaluating in vitro collagenase efficacy, other two pieces of plaque tissue were weighed and injected with type 1A collagenase (0.1 mg/100 mg tissue) or phosphate buffered saline (PBS) and maintained in incubator at 37°C for 72 hours in sterile conditions. After the incubation period, plaque fragments were again weighed and weight variation was determined Results When compared to normal TA, PD plaques expressed significantly higher amounts of TGFβ1 (1.30±0.37 vs. 0.47±0.20ng/ml, p<0.05), type 1 collagen (Col1; +337.9±89.4%, p<0.01), vimentin (+70.2±28.7%, p<0.05), β-catenin (+81.8±33.5%, p<0.05) and osteopontin (+42.1±18.1%, p<0.05) but not type 3 collagen (Col3). When plaques were segregated depending on response to in vitro collagenase injection (<20% or >20% weight reduction) it was revealed that plaques displaying poorer response had significantly higher contents of vimentin (+84.9±33.6%, p<0.05) and lower Col1/Col3 ratio (0.678±0.146 vs. 1.578±0.357, p<0.05) Conclusions Upregulation of vimentin, a cytoskeleton protein that confers cell structure resilience and influences biophysical properties of fibroblasts, could provide resistance of PD plaque to collagenase action. The activity of this enzyme might be also influenced by the relative amounts of different types of collagen in the plaque. PD might be a heterogeneous pathology and differences in plaque composition could determine therapeutic response to collagenase Disclosure No