Is α2-macroglobulin important in female stress urinary incontinence?

Background: Loss of mechanical stability of the urethra and bladder is thought to be important in the development of stress urinary incontinence (SUI). The vaginal wall is the main supporting tissue for pelvic organs and changes in components of supporting tissues are known to be involved in the pathophysiology of SUI. Methods: We evaluated changes in expression of alpha 2-macroglobulin (alpha 2-M), a protease inhibitor, in vaginal wall tissues from premenopausal women (aged 42-45 years) with SUI (n = 28) compared with menstrual cycle-matched continent women (controls, n = 29). The distribution of alpha 2-M in vaginal wall tissues and fibroblasts was analysed by immunohistochemistry and immunofluorescence. Expression levels of alpha 2-M mRNA and protein was determined by relative real-time quantitative PCR and enzyme-linked immunosorbent assay, respectively. Protease inhibition was measured to assess bioactivity. Results Vaginal wall tissues do express alpha 2-M. Expression of alpha 2-M mRNA and protein was significantly higher in tissues from controls compared to women with SUI in both proliferative and secretory phases (P<0.05). Protease inhibitory activity of alpha 2-M was significantly higher in tissues from controls compared to women with SUI in the secretory phase (P<0.05), but we found no difference in the proliferative phase between groups. alpha 2-M protein level was lower in the proliferative phase than the secretory phase in both controls and SUI patients, while for alpha 2-M mRNA this was found only in controls. Conclusions: Decreased expression of alpha 2-M mRNA and protein and protease inhibitory activity in the vaginal wall tissues of women with SUI may contribute to the development of SUI.