Vascular Endothelial Growth Factor Induces Endothelin-1 Production via Matrix Metalloproteinase-2 Rather than Endothelin-Converting Enzyme-1

• Published in: Hypertension in pregnancy Vol. 26; no. 2; pp. 189 - 199
• Main Authors: Lee, Kyung-Ju, Kim, Meyoung-Kon, Park, Yoon-Hee, Seol, Hyun-Joo, Lim, Ji-Eun, Lee, Jeong No, Oh, Min-Jeong
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.01.2007; Taylor & Francis
• Subjects: Adult; Analysis of Variance; Aspartic Acid Endopeptidases - antagonists & inhibitors; Aspartic Acid Endopeptidases - blood; Biomarkers - blood; Case-Control Studies; Dose-Response Relationship, Drug; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelin-1; Endothelin-1 - biosynthesis; Endothelin-1 - drug effects; Endothelin-converting enzyme-1; Endothelin-Converting Enzymes; Enzyme Inhibitors - blood; Enzyme Inhibitors - pharmacology; Enzyme-Linked Immunosorbent Assay; Female; Humans; Korea; Matrix Metalloproteinase 2 - blood; Matrix Metalloproteinase Inhibitors; Matrix metalloproteinase-2; Metalloendopeptidases - antagonists & inhibitors; Metalloendopeptidases - blood; Pre-Eclampsia - drug therapy; Pre-Eclampsia - metabolism; Preeclampsia; Pregnancy; Time Factors; Treatment Outcome; Umbilical Veins - cytology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1064-1955; 1525-6065
• DOI: 10.1080/10641950701204604

Objective: To investigate the mechanism of vascular endothelial growth factor (VEGF)-induced endothelin-1 production in human umbilical vein endothelial cells (HUVECs). Methods: Endothelin-1 levels were measured in conditioned medium of women with preeclampsia HUVECs were treated with different concentrations of VEGF165 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. Results: 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. Conclusion: These findings suggest that VEGF-induced endothelin-1 production might be mediated by MMP-2 rather than by ECE-1 upregulation.