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Original

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

, M.D., , M.D., , Ph.D., , M.D., , M.D., , M.D. & , M.D. show all
Pages 189-199 | Published online: 07 Jul 2009
 

Abstract

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.

Notes

*Presented at 25th Annual Meeting of the Society for Maternal-Fetal Medicine, Reno, Nevada, U.S.A. February 7–12, 2005.

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