Presentation Authors: Ingrid Harten, Stephen Evanko, Seattle, WA, Jay Choe, San Diego, CA, Eugene Lee, Hayward, CA, Marika Bogdani, Thomas Wight, Una Lee*, Seattle, WA
Introduction: Abnormal extracellular matrix (ECM) has been correlated with stress urinary incontinence (SUI). ECM components versican (VC) and hyaluronan (HA) play key roles in regulating tissue inflammation and maintaining connective tissue homeostasis. The objective of this study is to analyze the localization and expression of ECM components VC and HA in urethral and vaginal tissues in human clinical specimens and in a rat model of urinary incontinence.
Methods: Nulliparous Sprague-Dawley female rats underwent vaginal distension (VD), a rodent model of SUI, or a sham procedure. Tissues were harvested from 6 rats per group at days 1, 4, and 21 for immunohistochemistry and RNA expression analysis of ECM components. Urethral and vaginal samples from female patients with and without SUI were also examined.
Results: High intensity staining of VC was found in both sham and VD animals 1 day after surgery. This elevation persisted at day 4 in VD compared to sham, with concurrent reduced mRNA expression of VC degrading enzymes ADAMST 5 and 9 (Figure 1). Abundance of HA was not different between VD and sham, however mRNA expression of the HA synthase Has2 was significantly reduced in VD at day 4. Abundant versican staining was found in 60% of patient samples with SUI, which was strongest in regions of disrupted elastin.
Conclusions: Reduction of VC degrading enzymes and HA synthases at day 4 post surgery indicate a potential delay in ECM turnover associated with SUI. Abundant VC is associated with inflammation and elastin fiber network disruption, warranting further investigation to determine its role in the pathogenesis of SUI.
Source of Funding: Wilske Translational Research Program, Virginia Mason