Angiogenesis signaling in endometriosis: Molecules, diagnosis and treatment (Review)

Bo, Caixia; Wang, Yunfei

doi:10.3892/mmr.2024.13167

Cited by 4 publications

(2 citation statements)

References 134 publications

(238 reference statements)

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“…The stage of endometriosis was similar in both groups (p = 0.956). There were no demographic differences among the patients as age and BMI were similar in the two groups, with a median age of 38 years old (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)95%CIs) for the control group, who did not receive GnRH-a antagonists, and a median age of 35.5 years old (30-41, 95%CIs) (p = 0.388) for the experimental group, who did. The BMI was also identical between the two groups (p = 0.910).…”

Section: Resultsmentioning

confidence: 94%

“…Recent studies on the treatment of endometriosis have focused on the development of antiangiogenic drugs, such as anti-VEGF antibodies, VEGFR tyrosine kinase, COX-2 inhibitors, and dopamine agonists [44]. This is why the present study is of high originality, given the fact that it is the first time, to our knowledge, that a study has explored the impact of GnRH-a treatment preoperatively on angiogenetic pathways in women with endometriosis.…”

Section: Resultsmentioning

confidence: 97%

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The effect of GnRH-a on the angiogenesis of endometriosis

Filindris,

Papakonstantinou,

Keramida

et al. 2024

Hormones

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Purpose Neoangiogenesis is necessary for adhesion and invasiveness of endometriotic lesions in women affected by endometriosis. Vascular endothelial growth factor (VEGF) is one of the main components of angiogenesis and is part of the major pathway tissue factor (TF)-protease activated receptor-2 (PAR-2)-VEGF that leads to neoangiogenesis. Specificity protein 1 (SP1) is a transcriptional factor that has recently been studied for its crucial role in angiogenesis via a specific pathway. We hypothesize that by blocking angiogenetic pathways we can suppress endometriotic lesions. Gonadotrophin-releasing hormone-agonists (GnRH-a) are routinely used, especially preoperatively, in endometriosis. It would be of great interest to clarify which angiogenetic pathways are affected and, thereby, pave the way for further research into antiangiogenetic effects on endometriosis. Methods We used quantitative real-time polymerase chain reaction (qRT-PCR) to study mRNA expression levels of TF, PAR-2, VEGF, and SP1 in endometriotic tissues of women who underwent surgery for endometriosis and received GnRH-a (leuprolide acetate) preoperatively. Results VEGF, TF, and PAR-2 expression is significantly lower in patients who received treatment (p < 0,001) compared to those who did not, whereas SP1 expression is not altered (p = 0.779). Conclusions GnRH-a administration does affect some pathways of angiogenesis in endometriotic lesions, but not all of them. Therefore, supplementary treatments that affect the SP1 pathway of angiogenesis should be developed to enhance the antiangiogenetic effect of GnRH-a in patients with endometriosis. Trial registration Clinicaltrial.gov ID: NCT06106932.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 97%

The effect of GnRH-a on the angiogenesis of endometriosis

Filindris,

Papakonstantinou,

Keramida

et al. 2024

Hormones

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Cannabidiol as a possible treatment for endometriosis through suppression of inflammation and angiogenesis

Anvari Aliabad,

Hassanpour,

Norooznezhad

2024

Immunity Inflam & Disease

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BackgroundEndometriosis is associated with a wide variety of signs and symptoms and can lead to infertility, embryo death, and even miscarriage. Although the exact pathogenesis and etiology of endometriosis is still unclear, it has been shown that it has a chronic inflammatory nature and angiogenesis is also involved in it.ObjectiveThis review aims to explore the role of inflammation and angiogenesis in endometriosis and suggest a potential treatment targeting these pathways.FindingsAmong the pro‐inflammatory cytokines, studies have shown solid roles for interleukin 1β (IL‐β), IL‐6, and tumor necrosis factor α (TNF‐α) in the pathogenesis of this condition. Other than inflammation, angiogenesis, the formation of new blood vessels from pre‐existing capillaries, is also involved in the pathogenesis of endometriosis. Among angiogenic factors, vascular endothelial growth factor (VEGF), hypoxia‐inducible factor 1α (HIF‐1α), transforming growth factor β1 (TGF‐β1), and matrix metalloproteinases (MMPs) are more essential in the pathogenesis of endometriosis. Interestingly, it has been shown that inflammation and angiogenesis share some similar pathways with each other that could be potentially targeted for treatment of diseases caused by these two processes. Cannabidiol (CBD) is a non‐psychoactive member of cannabinoids which has well‐known and notable anti‐inflammatory and antiangiogenic properties. This agent has been shown to decrease IL‐1β, IL‐6, TNF‐α, VEGF, TGFβ, and MMPs in different animal models of diseases.ConclusionIt seems that CBD could be a possible treatment for endometriosis due to its anti‐inflammatory and antiangiogenic activity, however, further studies are needed.

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MMP-9 as a clinical marker for endometriosis: a meta-analysis and bioinformatics analysis

Huang,

Song,

Lei

et al. 2024

Front. Endocrinol.

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AimThis study systematically evaluated the potential efficacy of serum matrix metalloproteinase-9 (MMP-9) concentration as a diagnostic marker for endometriosis through meta-analysis. Early and accurate diagnosis of endometriosis, a common gynecological disease, is crucial for improving patient prognosis. Hence, this study aimed to comprehensively analyze the data from multiple studies to assess the diagnostic value of serum MMP-9 concentration for endometriosis.MethodsArticles investigating the association between MMP-9 and endometriosis, published from the inception of the databases until February 2024, were systematically retrieved from multiple databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and CNKI. Download and analyze the GSE7305, GSE23339, and GSE51981 datasets. Statistical analyses of all eligible studies were conducted using RevMan 5.4, Stata 11.0, and R software version 4.3.3.ResultsFifteen studies fully met the inclusion criteria for the meta-analysis. The concentration of MMP-9 in the blood of patients with endometriosis was significantly higher compared to that of the control group (p < 0.0001). Subgroup analysis based on different stages of endometriosis revealed a trend towards significantly higher serum MMP-9 concentrations in patients, whether in stages I-II or III-IV. Bioinformatics analysis revealed differences in the expression of MMP-9 in endometrial tissue between EMT patients and healthy controls in the GSE7305 and GSE23339 datasets. Additionally, in the GSE51981 dataset, we found significant differences between the normal group and both mild and severe cases of endometriosis.ConclusionBoth the current meta-analysis and bioinformatics analysis indicate differences in MMP-9 concentration levels between endometriosis patients and healthy individuals, with potentially elevated MMP-9 concentrations in serum samples from patients with endometriosis.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42024525864.

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Angiogenesis signaling in endometriosis: Molecules, diagnosis and treatment (Review)

Cited by 4 publications

References 134 publications

The effect of GnRH-a on the angiogenesis of endometriosis

The effect of GnRH-a on the angiogenesis of endometriosis

Cannabidiol as a possible treatment for endometriosis through suppression of inflammation and angiogenesis

MMP-9 as a clinical marker for endometriosis: a meta-analysis and bioinformatics analysis

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