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MMP and prolapse

Elaine Bronzatto, Cássio Luis Zanettini Riccetto
AIMS AND OBJECTIVES: Polypropylene meshes have been increasingly adopted for correction of pelvic organ prolapse due to its lower recurrence rate when compared to surgeries without meshes. The study of the interaction of these materials with the host tissue may contribute to the development of materials with best biocompatibility and, consequently, less complication rates. MATERIALS AND METHODS: The present study compares the inflammatory reaction of standard-weight (SW) and lightweight (LW) meshes (72 g/m216g/m2 respectively), implanted in the abdomen of 20 adult rats, which were euthanized in four or 30 days...
April 30, 2018: International Braz J Urol: Official Journal of the Brazilian Society of Urology
Antonella Vetuschi, Simona Pompili, Anna Gallone, Angela D'Alfonso, Maria Gabriella Carbone, Gaspare Carta, Claudio Festuccia, Eugenio Gaudio, Alessandro Colapietro, Roberta Sferra
Collagen and matrix metalloproteinases (MMP) play a pivotal role in the pathophysiology of Pelvic Organ Prolapse (POP) as a switch between type I and III collagen together with a simultaneous activation of MMPs have been observed in the vaginal wall. The aim of this study was to evaluate the Advanced Glycation End (AGE) products, ERK1/2 and transforming growth factor (TGF)-β/Smad pathway expression in muscularis propria in women with POP compared with control patients. We examined 20 patients with POP and 10 control patients treated for uterine fibromatosis...
May 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Yang Li, Li Hong, Cheng Liu, Jie Min, Shasha Hong, Ming Hu, Yang Zhao, Qing Yang, Jianming Tang, Songming He
The aim of the present study was to investigate the protective effect of puerarin on pelvic organ prolapse (POP) and the underlying mechanisms that regulate the metabolism of human parametrial ligament fibroblasts (HPLFs). HPLFs obtained from the pelvic tissue of patients with (n=10) or without (n=8) POP during hysterectomy were isolated by enzymatic digestion and subsequently identified by immunocytochemistry in a previous study of the authors. Following this, cultured HPLFs were treated with 0.01, 0.10 or 1...
February 2018: Molecular Medicine Reports
Sallie Oliphant, Timothy Canavan, Stacy Palcsey, Leslie Meyn, Pamela Moalli
BACKGROUND: Parity is the greatest risk factor for the development of pelvic organ prolapse. The normally supported vagina is pulled up and back over the levator ani. Loss of vaginal angulation has been associated with prolapse and may represent injury to the vaginal supportive tissues. OBJECTIVE: We proposed and examined the following hypotheses: (1) pregnancy and delivery impact vaginal support, leading to loss of vaginal angle; (2) vaginal angulation is restored postpartum; and (3) uncomplicated vaginal delivery (VD) is associated with accelerated remodeling of the vaginal fibrillar matrix...
February 2018: American Journal of Obstetrics and Gynecology
Meadow M Good, T Ignacio Montoya, Haolin Shi, Jun Zhou, YiHui Huang, Liping Tang, Jesus F Acevedo, R Ann Word
The pathophysiology and natural history of pelvic organ prolapse (POP) are poorly understood. Consequently, our approaches to treatment of POP are limited. Alterations in the extracellular matrix components of pelvic support ligaments and vaginal tissue, including collagen and elastin, have been associated with the development of POP in animals and women. Prior studies have shown the protease MMP-9, a key player of ECM degradation, is upregulated in vaginal tissues from both mice and women with POP. On the other hand, fibulin-5, an elastogenic organizer, has been found to inhibit MMP-9 in the vaginal wall...
2017: PloS One
Cheng Liu, Ying Wang, Bing-Shu Li, Qing Yang, Jian-Ming Tang, Jie Min, Sha-Sha Hong, Wen-Jun Guo, Li Hong
The present study aimed to reveal the metabolic alterations of the extracellular matrix (ECM) in uterosacral ligament (USL) with pelvic organ prolapse (POP) and to explore the role of transforming growth factor‑β1 (TGF‑β1) in pathogenesis of POP. For this purpse, 60 participants who underwent hysterectomy for benign indications were enrolled, 30 of which had symptomatic POP (grade II, III or IV) and composed the POP group, and the other 30 had asymptomatic POP (grade I or less) and served as the controls...
August 2017: International Journal of Molecular Medicine
Jie Min, Bingshu Li, Cheng Liu, Wenjun Guo, Shasha Hong, Jianming Tang, Li Hong
Pelvic organ prolapse (POP) is a global health problem that may seriously impact the quality of life of the sufferer. The present study aimed to investigate the potential mechanisms underlying alterations in extracellular matrix (ECM) metabolism in the pathogenesis of POP, by investigating the expression of ECM components in human parametrial ligament fibroblasts (hPLFs) subject to various mechanical strain loads. Fibroblasts derived from parametrial ligaments were cultured from patients with POP and without malignant tumors, who underwent vaginal hysterectomy surgery...
May 2017: Molecular Medicine Reports
Qifan Zhang, Cheng Liu, Shasha Hong, Jie Min, Qing Yang, Ming Hu, Yang Zhao, Li Hong
The regulation of the extracellular matrix (ECM) by mechanical stress is of interest as the ECM is essential in the development of pelvic organ prolapse. In the present study, the effect of overexposure to mechanical stress on the ECM, and the probable underlying mechanisms in cultured human uterosacral ligament fibroblasts (hUSLFs), was explored. Mechanical stress has an effect on oxidation‑antioxidation products in parametrial ligament fibroblasts. Thus, hUSLFs were incubated with different concentrations of hydrogen peroxide to elucidate any potential interactions...
January 2017: Molecular Medicine Reports
Charalampos Karachalios, Panagiotis Bakas, Georgios Kaparos, Styliani Demeridou, Ilias Liapis, Charalampos Grigoriadis, Aggelos Liapis
Pelvic organ prolapse (POP) is a common multifactorial condition. Matrix metalloproteinases (MMPs) are enzymes capable of breaking down various connective tissue elements. Single-nucleotide polymorphisms (SNPs) in regulatory areas of MMP-encoding genes can alter their transcription rate, and therefore the possible effect on pelvic floor supporting structures. The insertion of an adenine (A) base in the promoter of the MMP-3 gene at position -1612/-1617 produces a sequence of six adenines (6A), whereas the other allele has five (5A)...
September 2016: Biomedical Reports
Y Feng, Y Wang, B Yan, L Li, Y Deng
This meta-analysis was conducted to estimate the association between matrix metalloproteinase-1 (MMP-1) expression and pelvic organ prolapse (POP) in women. Relevant studies published before 6 December 2015 were identified by searching PubMed, Ovid, EBSCO, and EMBASE. A total number of five case-control studies, including 182 POP cases and 192 controls, were identified. The results indicated that women without POP had a lower MMP-1 level of expression compared with women with POP (odds ratio = 0.54, 95% confidence interval: 0...
August 19, 2016: Clinical and Translational Science
Kathleen Chin, Cecilia Wieslander, Haolin Shi, Sunil Balgobin, T Ignacio Montoya, Hiromi Yanagisawa, R Ann Word
Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5) during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO) mice were generated in which doxycycline (dox) treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i...
2016: PloS One
Alexis L Nolfi, Bryan N Brown, Rui Liang, Stacy L Palcsey, Michael J Bonidie, Steven D Abramowitch, Pamela A Moalli
BACKGROUND: Despite good anatomic and functional outcomes, urogynecologic polypropylene meshes that are used to treat pelvic organ prolapse and stress urinary incontinence are associated with significant complications, most commonly mesh exposure and pain. Few studies have been performed that specifically focus on the host response to urogynecologic meshes. The macrophage has long been known to be the key cell type that mediates the foreign body response. Conceptually, macrophages that respond to a foreign body can be dichotomized broadly into M1 proinflammatory and M2 proremodeling subtypes...
August 2016: American Journal of Obstetrics and Gynecology
Cheng Liu, Qing Yang, Gui Fang, Bing-Shu Li, De-Bin Wu, Wen-Jun Guo, Sha-Sha Hong, Li Hong
Pelvic organ prolapse (POP) is a global health problem, for which the pathophysiological mechanism remains to be fully elucidated. The loss of extracellular matrix protein has been considered to be the most important molecular basis facilitating the development of POP. Oxidative stress (OS) is a well‑recognized mechanism involved in fiber metabolic disorders. The present study aimed to clarify whether OS exists in the uterosacral ligament (USL) with POP, and to investigate the precise role of OS in collagen metabolism in human USL fibroblasts (hUSLFs)...
April 2016: Molecular Medicine Reports
M Victoria Estanol, Catrina C Crisp, Susan H Oakley, Steven D Kleeman, Angela N Fellner, Rachel N Pauls
OBJECTIVE: To evaluate systemic markers of collagen metabolism and vitamin C in female smokers with pelvic organ prolapse (POP). Secondary aims were to compare these levels in women based on prolapse or smoking history alone. STUDY DESIGN: This was a cross-sectional study with four groups: smokers with POP, non-smokers with POP, smokers without POP and non-smokers without POP. Subjects were age-matched based on smoking history and presence of POP. All underwent a fasting blood panel, including plasma procollagen 1-N propeptide (P1NP), matrix metalloproteinase 9 (MMP-9), and vitamin C...
January 2015: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Alejandra M Ruiz-Zapata, Manon H Kerkhof, Behrouz Zandieh-Doulabi, Hans A M Brölmann, Theo H Smit, Marco N Helder
Pelvic organ prolapse (POP) remains a great therapeutic challenge with no optimal treatment available. Tissue maintenance and remodelling are performed by fibroblasts, therefore altered cellular functionality may influence tissue quality. In this study, we evaluated functional characteristics of fibroblastic cells from tissues involved in POP. To rule out normal ageing tissue degeneration, biopsies from 18 premenopausal women were collected from the precervical region (non-POP site) after hysterectomy of 8 healthy and 10 POP cystocele cases (POP-Q stage ≥ II)...
November 2014: Molecular Human Reproduction
Ava Leegant, Lisa C Zuckerwise, Keith Downing, Jurriaan Brouwer-Visser, Changcheng Zhu, Maria Jose Cossio, Felix Strube, Xianhong Xie, Erika Banks, Gloria S Huang
OBJECTIVES: This study was undertaken to evaluate the expression of transforming growth factor β1 (TGF-β1) and matrix metalloproteinase 9 (MMP-9), key regulators of the extracellular matrix composition, in the uterosacral ligaments (USLs) of women with pelvic organ prolapse (POP) compared with controls. METHODS: Under an institutional review board approval, USL samples were obtained from women undergoing vaginal hysterectomy for stage 2 or greater POP (cases, n = 21) and from women without POP undergoing vaginal hysterectomy for benign indications (controls, n = 19)...
January 2015: Female Pelvic Medicine & Reconstructive Surgery
Rui Liang, Wenjun Zong, Stacy Palcsey, Steven Abramowitch, Pamela A Moalli
OBJECTIVE: The impact of polypropylene mesh implantation on vaginal collagen and elastin metabolism was analyzed using a nonhuman primate model to further delineate the mechanism of mesh induced complications. STUDY DESIGN: Forty-nine middle-aged parous rhesus macaques underwent surgical implantation of 3 synthetic meshes via sacrocolpopexy. Gynemesh PS (n = 12) (Ethicon, Somerville, NJ) and 2 lower-weight, higher-porosity, lower-stiffness meshes (UltraPro [n = 19] [Ethicon] and Restorelle [n = 8] [Coloplast, Minneapolis, MN]) were implanted, in which UltraPro was implanted with its blue orientation lines perpendicular (low stiffness direction, n = 11) and parallel (high stiffness direction, n = 8) to the longitudinal axis of the vagina...
February 2015: American Journal of Obstetrics and Gynecology
Xiaohong Wang, Yiqi Li, Jie Chen, Xiaoli Guo, Han Guan, Candong Li
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...
October 2014: Molecular Medicine Reports
David D Rahn, Meadow M Good, Shayzreen M Roshanravan, Haolin Shi, Joseph I Schaffer, Ravinder J Singh, R Ann Word
CONTEXT: Pelvic organ prolapse (POP) increases in prevalence with age; recurrence after surgical repair is common. OBJECTIVE: The objective of the study was to determine the effects of local estrogen treatment on connective tissue synthesis and breakdown in the vaginal wall of postmenopausal women planning surgical repair of POP. DESIGN: This was a randomized trial. SETTING: The study was conducted at an academic tertiary medical center...
October 2014: Journal of Clinical Endocrinology and Metabolism
Xiang Hu, Hao-Zhe Wang, Jun Liu, An-Qin Chen, Xiao-Feng Ye, Qiang Zhao
BACKGROUND: Increased sympathetic activity, commonly reported in mitral valve prolapse, indicates that the sympathetic nervous system might play an important role in regulating mitral interstitial cells. Hence, the aim of this study is to determine the level and pattern of adrenergic receptors expressed in human mitral valve leaflets and to investigate the effect of norepinephrine on physiologic behaviors of mitral interstitial cells. METHODS AND RESULTS: Immunohistochemistry displayed significantly increased expressions of β1, β2, and α1 adrenergic receptors in mitral valve prolapse...
2014: Circulation Journal: Official Journal of the Japanese Circulation Society
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