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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adult, Analysis of Variance, Aspartic Acid Endopeptidases, Biomarkers, Case-Control Studies, Dose-Response Relationship, Drug, Endothelial Cells, Endothelin-1, Endothelin-Converting Enzymes, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Female, Humans, Korea, Matrix Metalloproteinase 2, Matrix Metalloproteinase Inhibitors, Metalloendopeptidases, Pre-Eclampsia, Pregnancy, Time Factors, Treatment Outcome, Umbilical Veins, Vascular Endothelial Growth Factor A.
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Does vascular endothelial growth factor induce endothelin-1 production via matrix metalloproteinase-2 rather than endothelin-converting enzyme-1? Context: To investigate the mechanism of vascular endothelial growth factor (VEGF)-induced endothelin-1 production in human umbilical vein endothelial cells (HUVECs). Endothelin-1 levels were measured in conditioned medium of women with preeclampsia HUVECs were treated with different concentrations of VEGF(165) and at various time intervals. Next, we measured endothelin-1 levels after HUVECs were also incubated with VEGF and endothelin-converting enzyme-1 (ECE-1) inhibitor or tissue inhibitors of matrix metalloproteinase-2 (TIMP-2). Additionally, the circulating levels of total and free VEGF, matrix metalloproteinase-2 (MMP-2), and endothelin-1 were measured in 20 preeclamptic patients and 20 healthy pregnant controls. HUVECs treated with VEGF increased their endothelin-1 production in a concentration and time-dependent manner. The production of endothelin-1 was inhibited by TIMP-2, but not by the ECE-1 inhibitor. Total VEGF, MMP-2, and endothelin-1 concentrations were higher in preeclampsia and showed significant positive correlations between them.
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These findings suggest that VEGF-induced endothelin-1 production might be mediated by MMP-2 rather than by ECE-1 upregulation. Final Decision: yes