Vascular endothelial growth factor induces endothelin-1 production via matrix metalloproteinase-2 rather than endothelin-converting enzyme-1

Kyung Ju Lee, Meyoung Kon Kim, Yoon Hee Park, Hyun Joo Seol, Ji Eun Lim, Jeong No Lee, Min Jeong Oh

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)189-199
Number of pages11
JournalHypertension in Pregnancy
Volume26
Issue number2
DOIs
Publication statusPublished - 2007 Apr

Keywords

  • Endothelin-1
  • Endothelin-converting enzyme-1
  • Matrix metalloproteinase-2
  • Preeclampsia
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Internal Medicine
  • Obstetrics and Gynaecology

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