Immunoreactivity of Plasminogen Activator Inhibitor 1 and Its Correlation with Dysmenorrhea and Lesional Fibrosis in Adenomyosis

Yang, Bingxin; Gu, Ni-Hao; Shu, Shi; Zhang, Chen; Chen, Lan; Ouyang, Jing; Lin, Yeong-Jer; Sun, Feng; Xu, Hong

doi:10.1007/s43032-021-00513-6

Cited by 11 publications

(10 citation statements)

References 35 publications

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“…Adenomyosis, a chronic and refractory disease [15][16][17] , often leads to symptoms like heavy menstrual bleeding, severe dysmenorrhea, increased uterine size and infertility 18,19 . Despite its prevalence, the pathophysiology of adenomyosis remains poorly understood, hindering effective diagnosis and treatment.…”

Section: Discussionmentioning

confidence: 99%

Exosomal MiR-92a-3p serves as a Promising Diagnostic Marker and Potential Therapeutic Target for Adenomyosis

Shao,

Yu,

Wang

et al. 2024

Preprint

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This study aimed to elucidate the role of microRNA miR-92a-3p in the pathogenesis of adenomyosis. We focused on understanding how miR-92a-3p in exosomes derived from ectopic lesions influences the behavior of endometrial cells, DRG neurons, and Human Umbilical Vein Endothelial Cells (HUVECs), and its potential as a non-invasive diagnostic biomarker. Our findings revealed that MiR-92a-3p is significantly upregulated in exosomes derived from ectopic lesions of adenomyosis. This upregulation was associated with enhanced migration and invasion capabilities in eutopic endometrial cells, DRG neurons, and HUVECs. Furthermore, the study demonstrated a significant correlation between the levels of MiR-92a-3p in urinary exosomes and the clinical symptoms of adenomyosis, suggesting its potential as a non-invasive biomarker for the disease. This study elucidates an exosomal signaling process via miR-92a-3p that drives pathological infiltration and angiogenesis to promote adenomyosis progression. Upregulated miR-92a-3p in biofluid exosomes shows promising non-invasive biomarker potential for diagnosis and monitoring of this disease. Our findings unveil novel targets and tools for improved clinical management.Our research uncovers the significant role of miR-92a-3p in adenomyosis pathogenesis. We demonstrate that miR-92a-3p, upregulated in exosomes from ectopic lesions, enhances migration and invasion of endometrial cells, DRG neurons, and HUVECs. Crucially, miR-92a-3p levels in urinary exosomes correlate with adenomyosis symptoms, highlighting its potential as a non-invasive biomarker. This study offers new insights into adenomyosis progression and introduces novel diagnostic and therapeutic avenues.

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Section: Discussionmentioning

confidence: 99%

Exosomal MiR-92a-3p serves as a Promising Diagnostic Marker and Potential Therapeutic Target for Adenomyosis

Shao,

Yu,

Wang

et al. 2024

Preprint

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“…Studies have raised the possibility of an imbalance in coagulation factors playing a role in HMB in patients with endometriosis. Research has noted that women with endometriosis exhibit a hypercoagulable status characterized by elevated levels of specific coagulation factors, such as fibrinogen and vWF [ 17 – 19 , 53 , 54 ]. These elevated factors may contribute to HMB by promoting the formation of blood clots.…”

Section: Discussionmentioning

confidence: 99%

The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study

Liu

et al. 2023

BMC Med

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Background Endometriosis is recognized as a complex gynecological disorder that can cause severe pain and infertility, affecting 6–10% of all reproductive-aged women. Endometriosis is a condition in which endometrial tissue, which normally lines the inside of the uterus, deposits in other tissues. The etiology and pathogenesis of endometriosis remain ambiguous. Despite debates, it is generally agreed that endometriosis is a chronic inflammatory disease, and patients with endometriosis appear to be in a hypercoagulable state. The coagulation system plays important roles in hemostasis and inflammatory responses. Therefore, the purpose of this study is to use publicly available GWAS summary statistics to examine the causal relationship between coagulation factors and the risk of endometriosis. Methods To investigate the causal relationship between coagulation factors and the risk of endometriosis, a two-sample Mendelian randomization (MR) analytic framework was used. A series of quality control procedures were followed in order to select eligible instrumental variables that were strongly associated with the exposures (vWF, ADAMTS13, aPTT, FVIII, FXI, FVII, FX, ETP, PAI-1, protein C, and plasmin). Two independent cohorts of European ancestry with endometriosis GWAS summary statistics were used: UK Biobank (4354 cases and 217,500 controls) and FinnGen (8288 cases and 68,969 controls). We conducted MR analyses separately in the UK Biobank and FinnGen, followed by a meta-analysis. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out sensitivity analyses were used to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis. Results Our two-sample MR analysis of 11 coagulation factors in the UK Biobank suggested a reliable causal effect of genetically predicted plasma ADAMTS13 level on decreased endometriosis risk. A negative causal effect of ADAMTS13 and a positive causal effect of vWF on endometriosis were observed in the FinnGen. In the meta-analysis, the causal associations remained significant with a strong effect size. The MR analyses also identified potential causal effects of ADAMTS13 and vWF on different sub-phenotypes of endometrioses. Conclusions Our MR analysis based on GWAS data from large-scale population studies demonstrated the causal associations between ADAMTS13/vWF and the risk of endometriosis. These findings suggest that these coagulation factors are involved in the development of endometriosis and may represent potential therapeutic targets for the management of this complex disease.

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“…This mediator activates plasminogen, which is the enzyme responsible for the degradation of fibrin clots. In contrast, the eutopic endometrium and lesions of those with adenomyosis were found to have higher levels of the plasminogen activator inhibitor 1 (SERPINE1) -a PLAT inhibitor-when compared to healthy controls (62). Whether such aberrations result in less fibrinolysis or represent compensatory mechanisms remains to be determined.…”

Section: Pathology: Limiting Blood Lossmentioning

confidence: 96%

The Menstrual Endometrium: From Physiology to Future Treatments

Watters

Aguilar

Maybin

2022

Front. Reprod. Health

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Abnormal uterine bleeding (AUB) is experienced by up to a third of women of reproductive age. It can cause anaemia and often results in decreased quality of life. A range of medical and surgical treatments are available but are associated with side effects and variable effectiveness. To improve the lives of those suffering from menstrual disorders, delineation of endometrial physiology is required. This allows an increased understanding of how this physiology may be disturbed, leading to uterine pathologies. In this way, more specific preventative and therapeutic strategies may be developed to personalise management of this common symptom. In this review, the impact of AUB globally is outlined, alongside the urgent clinical need for improved medical treatments. Current knowledge of endometrial physiology at menstruation is discussed, focusing on endocrine regulation of menstruation and local endometrial inflammation, tissue breakdown, hypoxia and endometrial repair. The contribution of the specialised endometrial vasculature and coagulation system during menstruation is highlighted. What is known regarding aberrations in endometrial physiology that result in AUB is discussed, with a focus on endometrial disorders (AUB-E) and adenomyosis (AUB-A). Gaps in existing knowledge and areas for future research are signposted throughout, with a focus on potential translational benefits for those experiencing abnormal uterine bleeding. Personalisation of treatment strategies for menstrual disorders is then examined, considering genetic, environmental and demographic characteristics of individuals to optimise their clinical management. Finally, an ideal model of future management of AUB is proposed. This would involve targeted diagnosis of specific endometrial aberrations in individuals, in the context of holistic medicine and with due consideration of personal circumstances and preferences.

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Immunoreactivity of Plasminogen Activator Inhibitor 1 and Its Correlation with Dysmenorrhea and Lesional Fibrosis in Adenomyosis

Cited by 11 publications

References 35 publications

Exosomal MiR-92a-3p serves as a Promising Diagnostic Marker and Potential Therapeutic Target for Adenomyosis

Exosomal MiR-92a-3p serves as a Promising Diagnostic Marker and Potential Therapeutic Target for Adenomyosis

The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study

The Menstrual Endometrium: From Physiology to Future Treatments

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