Changes in extracellular matrix proteins in the cardinal ligaments of post-menopausal women with or without prolapse: a computerized immunohistomorphometric analysis

Ewies, Ayman

doi:10.1093/humrep/deg420

Cited by 132 publications

(108 citation statements)

References 26 publications

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“…Collagen is also the main organizational structural component connecting the pelvic organs (6). A number of studies have reported that collagen is involved in the pathogenesis of POP, and these studies have mainly focused on the collagen content, morphology and metabolism (7,8).…”

Section: Discussionmentioning

confidence: 99%

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Differential expression profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases in females with or without pelvic organ prolapse

Wang

Chen

et al. 2014

Molecular Medicine Reports

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Abstract. Pelvic organ prolapse (POP) is a common disorder that can disturb the health and quality of life of females. However, the basic pathophysiology and underlying mechanism of POP are not fully understood. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been reported to be associated with the onset and development of POP. In the present study, to characterize the differential expression profile of MMPs and TIMPs in female patients with and without POP, a total of 72 POP patients were sampled as a patient group and 72 non-POP patients that underwent hysterectomy due to benign tumors were sampled as a control group. Immunohistochemistry and polymerase chain reaction analysis were used to detect the expression levels of MMP-1, -2, -3 and -9 as well as TIMP-1 protein and mRNA in the anterior vaginal wall tissues. The expression levels of MMP-1, -2, -3 and -9 in the patient group were found to be significantly higher than those in the control group. By contrast, TIMP-1 expression levels in the patient group were significantly lower than those in the control group. Correlational analysis revealed a significantly positive correlation among the expression levels of MMP-2, -3 and -9. TIMP-1 expression levels were significantly negatively correlated with the expression levels of MMP-3 and -9. In addition, the expression levels of MMP-1 exhibited a positive correlation with those of MMP-2, -3 and -9, but a negative correlation with those of TIMP-1. The results demonstrated that the increased expression levels of MMPs and the reduced expression levels of TIMPs were directly associated with the presence of uterine prolapse, indicating that the differential expression levels of MMPs and TIMPs were correlated with the occurrence and development of POP. This data may assist in elucidating the molecular mechanism of MMP and TIMP involvement in POP, and also provide an underlying theoretical basis for the prevention and treatment of POP. IntroductionPelvic organ prolapse (POP) is the displacement of pelvic organs caused by various types of damage to the pelvic floor fascia and ligaments, which have failed to fully recover, or by weakened supporting structures, due to hypotonia. The predominant clinical manifestations are anterior and/or posterior vaginal wall prolapse as well as uterine prolapse (1). POP, a pelvic floor dysfunction (PFD) disorder, is a global health problem that affects 50% of parous females. It contributes to reduced quality of life and is a major reason for gynecological surgery in aging females (2). The pelvic organs are supported by pelvic floor muscles, the bony pelvis, ligaments and fascial supports. Abnormalities in the connective tissues of the pelvic support system have been suggested to contribute to the genesis of POP (3,4). The exact pathophysiology and natural history of POP, however, are not fully understood.The fascia and ligaments in the bladder and urethra are mainly composed of connective tissue, and the main structural protein is type I collagen...

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Section: Discussionmentioning

confidence: 99%

“…Collagen is also a structural protein in the extracellular matrix (ECM) and is responsible for the integrity of the pelvic floor structure (6). Recent studies have demonstrated that the content, components and ultrastructure of collagen are modified in the pelvic floor structure of POP patients (7).…”

Section: Introductionmentioning

confidence: 99%

Differential expression profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases in females with or without pelvic organ prolapse

Wang

Chen

et al. 2014

Molecular Medicine Reports

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“…Analysis of the cardinal ligaments reveals that 70-80% consists of collagen. 19 Collagen is thought to be one of the main determinants of biomechanical strength. There are approximately 28 types of collagen found in the human body, but the main subtypes in the pelvic floor are types I and III.…”

Section: Collagen Compositionmentioning

confidence: 99%

“…[20][21][22] Several studies have compared the amount of total and individual subtypes of collagen in the supporting ligaments and vaginal tissue of women with POP to a control group (see Table 1). 19,[23][24][25][26][27][28][29][30][31][32][33][34][35][36] Figure 1 Current anatomical considerations for prolapse. Level 1: The upper 1/3 of the vagina is suspended to the pelvic wall by the uterosacral and cardinal ligaments, condensations of endopelvic fascia.…”

Section: Collagen Compositionmentioning

confidence: 99%

Recent studies of genetic dysfunction in pelvic organ prolapse: The role of collagen defects

Lim

Khoo

Wong

et al. 2014

Aust NZ J Obst Gynaeco

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Gynaecologists are becoming increasingly aware that women with a family history of prolapse are at an increased risk of prolapse refractory to treatment. In the past five years, several genetic mutations have been shown to correlate with increased prolapse susceptibility. These mutations can result in disordered collagen metabolism, which weaken the fascial support of the pelvic organs. This review examines the contemporary evidence regarding the role of collagen in prolapse.

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“…Ewies et al (2003) and Karam et al (2007) demonstrated ) knockout mice with evidence of disrupted elastin fibers (Drewes et al, 2007). Lysyl oxidase-like1 (LOXL1) is a protein involved in the elastin fiber synthesis and assembly and LOXL1 knockout mice exhibit significant elastin fiber defects and POP in the postpartum period (Lee et al, 2008).…”

Section: Commentmentioning

confidence: 99%

Levormeloxifene inhibits vaginal tropoelastin and transforming growth factor beta 1 production

Takács

Yavagal

Zhang

et al. 2011

J. Smooth Muscle Res.

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Changes in extracellular matrix proteins in the cardinal ligaments of post-menopausal women with or without prolapse: a computerized immunohistomorphometric analysis

Cited by 132 publications

References 26 publications

Differential expression profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases in females with or without pelvic organ prolapse

Differential expression profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases in females with or without pelvic organ prolapse

Recent studies of genetic dysfunction in pelvic organ prolapse: The role of collagen defects

Levormeloxifene inhibits vaginal tropoelastin and transforming growth factor beta 1 production

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