Moreover, aminoguanidine can react directly with ROS, such as H2O2, hydroxyl radical and peroxynitrite

expression without significantly modifying mRNA levels in primary cell cultures of endometrial and 2901691 endometriotic stromal cells. miRNAs in Endometrial Cultures from Endometriosis establishment of endometriotic lesions. However, the specific mechanisms by which peritoneal fluid components modulate the expression of angiogenic and proteolytic factors in endometrial and endometriotic cells have not been previously elucidated. The present study shows that peritoneal fluid from women with endometriosis induces the highest decrease in angiogenesis-related miRNAs and the highest increase in VEGF-A protein levels in endometrial cell cultures from patients. The increase in protein levels without significant modification of mRNA levels could suggest a miRNA-mediated action on post-transcriptional regulation. miRNAs, which have emerged as important regulators of gene expression, are involved in most cellular processes and many diseases, including endometriosis. An increasing number of studies have described the relationship between miRNAs and angiogenesis and emerging data suggest that dysregulation of miRNA expression is involved in endometriosis, increasing the likelihood that miRNAs could be used as biomarkers and therapeutic tools for this disease. In the present study, treatment with peritoneal fluid resulted in decreased levels of miRNAs related to angiogenesis and an increase in VEGF-A protein levels. The six miRNAs assessed in this study were selected for this in vitro model because they regulate VEGF-A expression directly or indirectly. We found a significant 5 miRNAs in Endometrial Cultures from Endometriosis correlation between the decrease in miR-16 and the increase in VEGF-A in response to peritoneal fluid exposure in endometrial and endometriotic cell cultures. This correlation could indicate regulation of VEGF-A translation by miR-16. 9504387 It has been shown that VEGF-A is a target gene for miR-16 in several cell types, indicating that miR-16 could be an important regulator of angiogenesis. However, further experiments would be needed to test the hypothesis. Furthermore, a significant inverse correlation was observed after peritoneal fluid treatment between the increase in VEGF-A protein expression and miR-17-5p, miR-20a, miR-125a and miR222 levels in endometriotic cell cultures. These results suggest that peritoneal fluid modulates angiogenesis in endometrial and endometriotic stromal cells via miRNA action. miRNAs -17-5p and -20a are contained in the miR-17-92 cluster, which has a complex role in angiogenesis. While miR-17-5p, has pro-angiogenic activity, miR-20a displays anti-angiogenic activity by targeting VEGF-A. Recently, Doebele et al. showed that miR-17 and miR-20a exhibit a cell-intrinsic anti-angiogenic activity in endothelial cells. Another angiomiRs, miR-221 and miR-222, with a demonstrated anti-angiogenic activity by targeting c-kit, have been shown to TG-101348 site inhibit endothelial cell migration, proliferation, and angiogenesis in vitro. Several groups have studied peritoneal-endometrial interactions, showing that peritoneal fluid components play an important role in the pathogenesis of endometriosis. Moreover, cell types such as macrophages and endometrial and red blood cells have been detected in peritoneal fluid. Endometriotic peritoneal fluid reportedly induces the production and release of VEGF by neutrophils. Our data show that endometriotic peritoneal fluid induced the highest increase in VEGF-A protein levels and the lowest m