Elastolytic activity in women with stress urinary incontinence and pelvic organ prolapse.
OBJECTIVE
Weakening of pelvic supportive tissues is thought to be a contributing etiology in female pelvic floor disorders such as stress urinary incontinence and/or pelvic organ prolapse (SUI/POP). Since elastin modulates the mechanical properties of supportive tissues, we examined elastase activity in vaginal tissue from women with pelvic floor dysfunction compared to asymptomatic controls, by comparing overall elastase activity, human neutrophil elastase, cathepsin K, and alpha-1 antitrypsin (a serine protease inhibitor) mRNA and protein levels.


METHODS
Full-thickness peri-urethral vaginal wall tissues were collected from age and menstrual-phase matched SUI/POP and control women at the time of pelvic surgery. Elastolytic activity in the homogenized tissue was determined by the generation of amino groups from succinylated elastin. To quantify mRNA levels of each protein, quantitative competitive-PCR and confirmatory Western blot analyses were performed on the samples for human neutrophil elastase, cathepsin K, and alpha-1 antitrypsin.


RESULTS
The mean elastolytic activity in vaginal tissues from the SUI/POP group was similar to that in the control group. With respect to the proteolytic enzymes, neither human neutrophil elastase nor cathepsin K differed between the two groups. However, alpha-1 antitrypsin mRNA and protein levels were significantly decreased in tissues from affected women.


CONCLUSIONS
A significant decrease in alpha-1 antitrypsin expression was seen in tissues from women with SUI/POP compared to controls. This data suggest that altered elastin metabolism may contribute to the connective tissue alterations observed in pelvic floor dysfunction. Future investigations are warranted to help define the role of elastin turnover in pelvic floor dysfunction.
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317, USA. bchen@stanford.edu
Bertha
B
Chen
Yan
Y
Wen
Mary Lake
ML
Polan
D000328:Adult; D056657:Cathepsin K; D002403:Cathepsins / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D017697:Premenopause; D014550:Urinary Incontinence, Stress / Q000201:enzymology*; D014596:Uterine Prolapse / Q000201:enzymology*; D014621:Vagina / Q000737:chemistry; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000378:metabolism*
D000515:alpha 1-Antitrypsin; D002403:Cathepsins; D019272:Leukocyte Elastase; C534130:CTSK protein, human; D056657:Cathepsin K