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Molecular diagnosis of endometriosis
Published in Carlos Simón, Linda C. Giudice, The Endometrial Factor, 2017
Lusine Aghajanova, Linda C. Giudice
A key mechanism for endometrial cell survival in ectopic locations is establishing a blood supply (130). This process (neoangiogenesis) occurs concomitantly with neuronal sprouting, and the two together comprise neuroangiogenesis (131). It is supported by high levels of vascular endothelial growth factor (VEGF) and other angiogenic factors in peritoneal fluid and endometrium from women with endometriosis compared with healthy controls (132–135). Endothelial endometrial cells from women with endometriosis also express higher proliferation ability and distinct gene expression patterns compared with nonendometriosis controls (136). A transcript for pleiotrophin, an angiogenesis-associated peptide, was significantly upregulated in eutopic endometrium from women with severe endometriosis (137); however, its usefulness as a potential marker has not been evaluated. Pro-angiogenic E2-regulated Cyr61 has been proposed as a potential cycle-independent marker of endometriosis (see above and (77)).
CD73+ extracellular vesicles inhibit angiogenesis through adenosine A2B receptor signalling
Published in Journal of Extracellular Vesicles, 2020
Roberta Angioni, Cristina Liboni, Stephanie Herkenne, Ricardo Sánchez-Rodríguez, Giulia Borile, Elisabetta Marcuzzi, Bianca Calì, Maurizio Muraca, Antonella Viola
EVs are defined as heterogeneous plasma membrane vesicles, classified mainly by their size and cargo [29] that can be released from various cell types [30]. It has been reported that MSC-derived EVs enhance, for instance, the neovascularization after ischaemic injury in a rat myocardial infarction model [31]. Similarly, they increased postischemic neuroangiogenesis after focal cerebral ischaemia in mice [32]. In most cases, precise mechanisms by which EVs exert their functions remain to be elucidated. However, a recent proteomic analysis reveals that MSC-derived EVs are strongly enriched in several proangiogenic signalling associated proteins, such as epithelial growth factor (EGF), FGF and PDGF [33]. Furthermore they can transfer pro-angiogenic miRNAs, such as the pro-angiogenic miR-126, miR-130a [34] and miR-125 [35,36], as well as signalling proteins and transcription factors [28].
Advances in targeting estrogen synthesis and receptors in patients with endometriosis
Published in Expert Opinion on Investigational Drugs, 2022
Sara Clemenza, Silvia Vannuccini, Agostino Ruotolo, Tommaso Capezzuoli, Felice Petraglia
Currently, hormonal therapies are the most effective drugs for the treatment of endometriosis. Progesterone resistance and increased production and sensitivity to estrogens are the most relevant mechanisms on which hormonal treatments interfere [10]. First-line therapy for endometriosis is represented by progestins, which act on progesterone resistance, inflammation, neuroangiogenesis and ectopic cell proliferation [11]. Since estrogens play a crucial role in the pathogenesis of endometriosis, it is reasonable to consider lowering their concentrations as a therapeutic goal. Progestins act also indirectly on estrogen-mediated mechanisms, by interfering with enzymes involved in estrogens synthesis and metabolism, resulting in the ERs downregulation and local E2 reduction [11]. Inhibition of estrogen production is one of the targets of available and emerging drugs for endometriosis, such as gonadotropin-releasing hormone analogs (GnRH-a), GnRH antagonists, and aromatase inhibitors (AIs) [10]. Nevertheless, all these treatments are often associated with hypoestrogenic side effects and even though they may control endometriosis symptoms, they cannot prevent or definitively treat the disease. Furthermore, they are not appropriate for patients who wish to conceive. Therefore, the goal of emerging treatments should be to ensure long-term benefit on pain symptoms, with few side effects and possibly without contraceptive action [2,10]. Considering the information above, drugs targeting ERs represent a promising treatment option, as they may induce a more specific inhibition of disease activity within endometriotic implants, avoiding prolonged hypoestrogenic status and limiting systemic adverse effects. The present review aims to summarize available and emerging treatments that interfere, through central or local mechanisms, with the typical estrogen dependence of endometriosis, focusing also on innovative molecules which exert a direct action on ERs.