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• W2148743089 startingPage "2819" @default.
• W2148743089 abstract "Objective— The purpose of this study is to investigate the expression and regulation of type-2 tissue factor pathway inhibitor (TFPI-2) in endothelial cells, as well as the regulation of human endothelial cell (EC) function by TFPI-2. Methods and Results— Real-time polymerase chain reaction (PCR) and Western blot analysis revealed that vascular endothelial growth factor (VEGF) induced both time- and dose-dependent increase in TFPI-2 mRNA and protein expression in endothelial cells. TFPI-2 mRNA expression was also significantly upregulated by IL-1β, and modestly increased by both tumor necrosis factor (TNF)-α and fibroblast growth factor (FGF)-2, but not placental growth factor (PlGF). VEGF upregulation of TFPI-2 was dramatically reduced by inhibition of the MEK pathway. Administration of TFPI-2 protein suppressed both VEGF and FGF-2 stimulation of EC proliferation in a dose-dependent manner. A recombinant preparation of the first Kunitz-type domain of TFPI-2 (KD1) did not suppress growth factor stimulation of EC proliferation, suggesting a mechanism distinct from the proteinase inhibitory activity of TFPI-2. Exogenously added TFPI-2 protein suppressed VEGF-induced EC migration in 2 different assays. Recombinant wt-KD1 or the R24K mutant of KD1, but not the R24Q mutant, dramatically suppressed VEGF-induced EC migration. TFPI-2 protein, but not recombinant KD1, blocked VEGF-induced activation of both Akt and ERK1/2 in ECs. At higher doses, TFPI-2 protein blocked VEGFR2 activation. Conclusion— Our data suggest that VEGF-upregulation of TFPI-2 expression in endothelial cells may represent a mechanism for negative feedback regulation and modulation of its pro-angiogenic action on endothelial cells. TFPI-2, or derivatives of TFPI-2, may be novel therapeutics for treatment of angiogenic disease processes." @default.
• W2148743089 created "2016-06-24" @default.
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• W2148743089 date "2006-12-01" @default.
• W2148743089 modified "2023-09-25" @default.
• W2148743089 title "Tissue Factor Pathway Inhibitor-2 Is Upregulated by Vascular Endothelial Growth Factor and Suppresses Growth Factor-Induced Proliferation of Endothelial Cells" @default.
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• W2148743089 doi "https://doi.org/10.1161/01.atv.0000248731.55781.87" @default.
• W2148743089 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17023682" @default.
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