Circulating matrix metalloproteinases and their tissue inhibitors as markers for ethnic variation in pelvic floor tissue integrity

Abstract

Abstract. The purpose of the present study was to measure the plasma levels of matrix metalloproteinases (MMP)-2 and -9 and their tissue inhibitors (TIMP)-1 and -2, as surrogate biomarkers for pelvic floor tissue integrity in young, healthy multi-ethnic women. This was hoped to elucidate ethnic vulnerability to support-related pelvic floor dysfunctions. The plasma levels of MMP-2 and -9 and TIMP-1 and -2 were measured by sandwich ELISA in nulliparous, young (18-29 years) women volunteers (n=85) from five ethnic groups [n=17/group; Bahrainis, other Arabs, Filipinos, Indians/Pakistanis and Caucasians (Italians)] and compared with levels in Italians as the reference group. It was identified that the levels of plasma MMP-2 were significantly higher in Italians than in Bahrainis (P<0.001) and Filipinos (P<0.001), but significantly lower than in Indians/Pakistanis (P=0.013); whereas, the levels of plasma MMP-9 were significantly higher in Italians than in Bahrainis (P=0.009) and Indians/Pakistanis (P<0.015). The levels of plasma TIMP-2 were significantly lower in Italians than in Indians/Pakistanis (P=0.003), but the levels of plasma TIMP-1 were significantly higher in Italians than in all other groups (P<0.05) excluding Bahrainis. Although MMP-2 correlated negatively with TIMP-2 and MMP-9 correlated positively with TIMP-1, both correlations were not significant (r=0. 071, P=0.533 and r=0.197, P=0.8, respectively). In all ethnic groups, MMP-9 level correlated positively with BMI (r=0.26, P=0.02), and TIMP-2 level with age (r=0.23, P=0.045). Overall, the trends for higher levels of MMP-2 and -9 and lower levels of TIMP-2 in the plasma of Caucasian women may indicate a greater tendency for collagenolysis and weaker connective tissue with increased risk of developing pelvic floor dysfunctions, and thus may potentially serve as biomarkers for pelvic floor tissue integrity. IntroductionSupport-related pelvic floor dysfunctions including pelvic organ prolapse (POP), stress urinary incontinence (SUI) and faecal incontinence are caused by structural defects in the complex supportive apparatus formed by the connective tissue and striated muscles of the pelvic floor (1-7). The role of the connective tissue component is to counteract both stretch and compression of the pelvic floor exerted by the gravitational and inertial forces of the intra-abdominal pressure and to repair damaged tissues (2,4,6). This supportive function is determined by the tensile strength of collagen in the extracellular matrix that is maintained by continuous remodelling of collagen (1,3). The latter depends on a critical balance between collagen degradation and production that is controlled by a group of enzymes, matrix metalloproteinases (MMPs) and their respective tissue inhibitors (TIMPs) (1,3,5). The prevalence of support-related pelvic floor dysfunctions is affected by racial and ethnic origin, with a higher risk observed in Caucasians than in other populations (8)(9)(10). This may be explained by genetic, environmental and/or anatomical difference...