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- W2049854504 abstract "Recently, increased circulating levels of soluble fms-like tyrosine kinase 1 (sFlt1) and decreased circulating levels of free vascular endothelial growth factor (VEGF) have been demonstrated in patients with preeclampsia and suggested as a mechanism of endothelial dysfunction in preeclampsia. However, an incubation of myometrial resistance vessels with VEGF resulted in a reduction of endothelium-dependent relaxation. VEGF has been known to upregulate endothelin-converting enzyme-1 (ECE-1), a key enzyme for endothelin-1(ET-1)[1-21] processing. However, matrix metalloproteinase-2 (MMP-2) can also cleave big endothelin-1 and yield more potent ET-1[1-32]. The purpose of this study is to determine the mechanism of VEGF-induced, endothelium-dependent inhibition of vasorelaxation using human umbilical vein endothelial cells (HUVECs). HUVECs were first incubated for 24h in serum-free medium at 37°C and 5% CO2.The medium was replaced with medium containing various concentrations (0.1, 1, and 10 ng/mL) of recombinant VEGF165 and the cultures were further incubated for 6-48 hrs. The cells were then incubated with phosphoramidon (known as endothelin-converting enzyme-1 inhibitor) or tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) in the presence of 10 ng/mL of VEGF. The cell-free supernatant was then aliquoted and stored frozen at −80°C and assayed for ET-1 using ELISA kit. ET-1 levels could be detected in the culture media using ELISA kit and increased in the media of VEGF treated HUVECs in dose-dependent and time-dependent manner compared with untreated cells. The ET-1 levels in the media were decreased not by phosphoramidon but by TIMP-2 after 48 hours incubation. These findings suggest that VEGF-induced, endothelium-dependent inhibition of vasorelaxation might be mediated by increased ET-1 via MMP-2 upregulation." @default.
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- W2049854504 date "2004-12-01" @default.
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- W2049854504 title "Vascular endothelial growth factor upregulates the expression of endothelin-1 by matrix metalloproteinase-2 in huvecs" @default.
- W2049854504 doi "https://doi.org/10.1016/j.ajog.2004.10.004" @default.
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