Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS

Published on Jan 5, 2016in Reproduction3.206
· DOI :10.1530/REP-15-0340
Javad Ranjbaran1
Estimated H-index: 1
Marzieh Farimani5
Estimated H-index: 5
+ 4 AuthorsIraj Khodadadi18
Estimated H-index: 18
It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53±15.32 vs 44.61±18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.
📖 Papers frequently viewed together
8 Citations
49 Citations
Context: Adrenal hyperandrogenism affects approximately 25% of polycystic ovary syndrome (PCOS) patients but its relation to obesity is not totally understood. Objective: This study aimed to assess dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) levels in relation to body mass index (BMI) in PCOS. Design and Setting: This was a prospective observational study at an institutional practice at an obstetrics/gynecology hospital. Participants: The study included 136 PCOS pati...
35 CitationsSource
#1Sarantis Livadas (UoA: National and Kapodistrian University of Athens)H-Index: 24
#2Anastasios Kollias (UoA: National and Kapodistrian University of Athens)H-Index: 30
Last. Evanthia Diamanti-Kandarakis (UoA: National and Kapodistrian University of Athens)H-Index: 62
view all 4 authors...
Background: Polycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with the syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging. Objective: To evaluate the chang...
26 CitationsSource
#1Sandrine Bouchet (UPMC: Pierre-and-Marie-Curie University)H-Index: 15
#2Brigitte Bauvois (UPMC: Pierre-and-Marie-Curie University)H-Index: 29
Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemi...
35 CitationsSource
#1Maria Grazia Porpora (Sapienza University of Rome)H-Index: 24
#2Federica Tomao (Sapienza University of Rome)H-Index: 25
Last. Giuseppe Benagiano (Sapienza University of Rome)H-Index: 36
view all 8 authors...
Background: Aim of this prospective, case–control study was to evaluate uterine arteries’ blood flow before and after laparoscopic surgery in patients with ovarian endometriosis and its possible correlation with infertility. Methods: We prospectively enrolled 110 women of reproductive age; 69 with ovarian endometriomas and scheduled for surgery, and 41 controls. At enrolment, a detailed medical, gynecologic and obstetric history was collected. Fertility and pregnancy desire were assessed. All pa...
69 CitationsSource
#1Gillian Murphy (University of Cambridge)H-Index: 134
The present invention provides a nucleic acid sequence which encodes a novel tissue inhibitor of metalloproteinases (TIMP-4) which was isolated from cells of human uterus. The invention provides for genetically engineered expression vectors and host cells comprising nucleic acid sequence encoding TIMP-4. The invention also provides for purified TIMP-4.
305 CitationsSource
#1Hung-Chin TsaiH-Index: 14
#2Shin Yu Ye (KMU: Kaohsiung Medical University)H-Index: 1
Last. Yao Shen Chen (NYMU: National Yang-Ming University)H-Index: 25
view all 9 authors...
Abstract The potential mechanisms for altered matrix metalloproteinase (MMP) or tissue inhibitors of matrix metalloproteinase (TIMP) function in patients with syphilis and HIV-1 co-infection (HIV-S) was unclear. To determine the expression of MMP-2, 9 and TIMP-1, 2, 4 in the serum and cerebrospinal fluid (CSF) of HIV-S patients, a total of 20 HIV-S patients and 8 controls were enrolled in a HIV-1 clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of MMP-2, 9, ...
10 CitationsSource
#1Valeria A. Gomes (State University of Campinas)H-Index: 8
#2Carolina Sales Vieira (USP: University of São Paulo)H-Index: 20
Last. Jose E. Tanus-Santos (USP: University of São Paulo)H-Index: 63
view all 8 authors...
Altered levels of matrix metalloproteinases (MMPs) may reflect relevant pathogenetic mechanisms of disease conditions. The objective of this study was to compare the plasma levels of MMPs and tissue inhibitors of MMPs (TIMPs) in polycystic ovary syndrome (PCOS) patients with those found in healthy ovulatory controls and to examine whether the levels of these biomarkers are associated with clinical and biochemical features of this syndrome. Sixty-five healthy ovulatory subjects (controls) and 80 ...
24 CitationsSource
#2Mesut Ozkaya (Imam Muhammad ibn Saud Islamic University)H-Index: 16
Last. Yusuf Üstün (İnönü University)H-Index: 18
view all 4 authors...
Background: Our aim was to investigate levels of lipocalin-2 and its relationship with metabolic factors in women with polycystic ovary syndrome (PCOS). Materials/Subjects and methods: In this cross-sectional study, two groups of women were studied: group 1 consisted of women with PCOS (no.=30), and group 2 consisted of control women with normal ovulatory function (no.=30). The circulating levels of free testosterone (T), DHEAS, glucose, insulin, triglycerides (TG), HDL, LDL and lipocalin were m...
28 CitationsSource
#1Stavroula BakaH-Index: 19
#2Konstantina ZourlaH-Index: 2
Last. George CreatsasH-Index: 38
view all 8 authors...
The present study was undertaken to investigate the levels of matrix metalloproteinase (MMP)-2, MMP-9 and their tissue inhibitors (TIMP-2 and TIMP-1, respectively) in the follicular fluid of 39 patients with polycystic ovary syndrome (PCOS) and compare them with the levels found in 56 age- and weight-matched normally ovulating women, all undergoing in vitro fertilisation (IVF) treatment. Significantly higher levels of MMP-2 and MMP-9 (p=0.02 and p<0.001, respectively) as well as TIMP-2 and TIMP-...
24 Citations
#1Davide Bolignano (UNIME: University of Messina)H-Index: 33
#2Valentina Donato (UNIME: University of Messina)H-Index: 13
Last. Michele Buemi (UNIME: University of Messina)H-Index: 54
view all 7 authors...
The small 25 kDa peptide, neutrophil gelatinase-associated lipocalin (NGAL), first known as an antibacterial factor of natural immunity, and an acute phase protein, is currently one of the most interesting and enigmatic proteins involved in the process of tumor development. The aim of the present review is to point out the main contradictory, sometimes even paradoxical, effects attributed to NGAL in human neoplasias. For instance, acting as an intracellular iron carrier and protecting MMP9 from ...
143 CitationsSource
Cited By18
#1Liyun Duan (Peking Union Medical College)H-Index: 2
#2De Jin (Peking Union Medical College)H-Index: 5
Last. Fengmei Lian (Peking Union Medical College)H-Index: 14
view all 10 authors...
Background. Rhizoma coptidis (RC) showed a significant effect on PCOS, but its mechanism in PCOS remains unclear. Methods. The components of RC were searched by TCMSP. The Smiles number of the active ingredients was queried through PubChem, and the predicted targets were obtained from the SwissTargetPrediction database. The DrugBank, GeneCards, and DisGeNET databases were retrieved to acquire the related targets of PCOS. Then, the network of compound-target was constructed. The core targets were...
#1Alzbeta Mlynarcikova (SAV: Slovak Academy of Sciences)H-Index: 10
#2Sona Scsukova (SAV: Slovak Academy of Sciences)H-Index: 12
Abstract null null While Bisphenol A (BPA) has been a requisite plastic additive, as an endocrine disruptor it has been associated with adverse health effects including ovarian disorders. Following implemented restrictions on BPA usage, it is replaced by alternative bisphenols, biological effects of which have not been adequately investigated. Our study examined effects of bisphenols AF (BPAF) and S (BPS), on the human ovarian granulosa cell line COV434, and compared them with BPA, with the focu...
#1Alzbeta Mlynarcikova (SAV: Slovak Academy of Sciences)H-Index: 10
#2Sona Scsukova (SAV: Slovak Academy of Sciences)H-Index: 12
In order to replace industrial functions of the restricted endocrine disruptor bisphenol A (BPA), its structural analogs are increasingly employed without adequate assessment of their biological actions. Our study examined effects of the bisphenols AF (BPAF), S (BPS) and F (BPF), on functions of porcine ovarian granulosa cells (GCs) with the focus on viability, steroid production (10-9-10-4M), and expression of factors (10-9-10-5M) important for the follicle development: vascular endothelial gro...
1 CitationsSource
#1Abu Saleh Md Moin (Khalifa University)H-Index: 10
#2Thozhukat Sathyapalan (Hull York Medical School)H-Index: 27
Last. Stephen L. Atkin (RCSI: Royal College of Surgeons in Ireland)H-Index: 59
view all 4 authors...
Background. Women with polycystic ovary syndrome (PCOS) often have vitamin D deficiency, a known risk factor for severe COVID-19 disease. Alveolar macrophage-derived cytokines contribute to the inflammation underlying pulmonary disease in COVID-19. We sought to determine if basal macrophage activation, as a risk factor for COVID-19 infection, was present in PCOS and, if so, was further enhanced by vitamin D deficiency. Methods. A cross-sectional study in 99 PCOS and 68 control women who presente...
1 CitationsSource
Abstract Introduction Studies investigating the relationship between sex hormones, inflammatory mediators and joint disorders have reported that sex hormones affect the pathogenesis of joint disorders. We aimed to investigate temporomandibular joint disorder (TJD) in polycystic ovary syndrome (PCOS) and the possible role of systemic mediators and sex hormones in TJD pathogenesis. Material and methods PCOS patients (n = 45) and controls (n = 30) aged 20–40 years, were enrolled in this case-contro...
Reactive Oxygen Species Modulator 1 (ROMO1) plays a pivotal role in the regulation of mitochondrial structure integrity, and the production of reactive oxygen species (ROS). Increased ROMO1 expression was reported in various cancer cell lines; however, the possible association between ROMO1 expression and bladder cancer was not well studied. The present study aimed to investigate the rate of ROMO1 expression and the correlation of oxidative stress with the development of bladder cancer. In this ...
1 CitationsSource
#1Susan Idicula-Thomas (National Institute for Research in Reproductive Health)H-Index: 16
#2Ulka Gawde (National Institute for Research in Reproductive Health)H-Index: 1
Last. Gary D. Bader (U of T: University of Toronto)H-Index: 98
view all 5 authors...
Abstract Polycystic ovary syndrome (PCOS) is a complex multigenic disorder and women with PCOS suffer from several comorbidities. Although, obesity is a known risk factor for PCOS, the incidence of lean women with PCOS is on the rise. A systematic and comparative study on lean and obese PCOS with respect to genes, pathways and comorbidity analysis has not been attempted so far. Analysis of differentially expressed genes (DEGs) across tissue types for lean and obese PCOS revealed that the majorit...
BACKGROUND: Glaucoma is the irreversible vision loss and contributes second leading cause of blindness worldwide. Matrix metalloproteinase-9 (MMP-9) is involved with remodeling and destruction of extracellular matrix. Elevated MMP-9 levels and various functional variants of MMP-9 have been associated with glaucoma in different population. In the current investigation, we tested association of MMP-9 common variants with different clinical categories of glaucoma in Chinese population. MATERIALS AN...
2 CitationsSource
#1Wenting Xu (Nanjing University of Chinese Medicine)H-Index: 4
#2Mengyu Tang (Nanjing University of Chinese Medicine)H-Index: 2
Last. Lihong Wang (Nanjing University of Chinese Medicine)H-Index: 5
view all 4 authors...
Background. Polycystic ovary syndrome (PCOS) is the most common female endocrine disease. Cangfu Daotan Decoction (CDD) can effectively relieve the clinical symptoms of PCOS patients. Methods. To explore the active ingredients and related pathways of CDD for treating PCOS, a network pharmacology-based analysis was carried out. The active ingredients of CDD and their potential targets were obtained from the TCM system pharmacology analysis platform. The obtained PCOS-related genes from OMIM and G...
7 CitationsSource
#1Eva Vargas (University of Jaén)H-Index: 1
#2Lusine Aghajanova (Stanford University)H-Index: 26
Last. Francisco J. Esteban (University of Jaén)H-Index: 33
view all 5 authors...
Abstract Research question Women with endometriosis are considered to be at higher risk of several chronic diseases, such as autoimmune disorders, gynecologic cancers, asthma/atopic diseases, cardiovascular and inflammatory bowel diseases. Could the study of endometriosis-associated comorbidities help to identify potential biomarkers and target pathways of endometriosis? Design We performed a systematic review in order to identify all possible endometriosis-associated comorbid conditions. Next, ...
2 CitationsSource