Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2582826 | Environmental Toxicology and Pharmacology | 2016 | 6 Pages |
•We treated Human Umbilical Vein Endothelial Cells (HUVECs) with arsenite.•Arsenite suppressed the angiogenesis of HUVECs in a dose-dependent manner.•We treated HUVECs with E7080 and CP-673451.•E7080 completely prevented and CP-673451 significantly decreased the angiogenesis.•We also found that arsenite suppressed the angiogenesis mediated by PDGFR-beta.
The present study aimed to investigate the effects of sodium arsenite (NaAsO2) on the angiogenesis of human umbilical vein endothelial cells (HUVECs) and the mechanism involved. Firstly, a Matrigel-based in vitro angiogenesis assay demonstrated that arsenite suppressed the angiogenesis of HUVECs in a dose-dependent manner. Then by using a global inhibitor for multiple growth factor receptors (E7080) and a specific inhibitor of PDGFR-beta (CP-673451), we found that E7080 completely prevented and CP-673451 significantly decreased the angiogenesis of HUVECs. This suggested that angiogenesis of HUVECs depends on the signal pathway mediated by tyrosine kinase receptors and that among them, PDGFR-beta has an important regulatory function. Finally by using porcine aortic endothelial cells which stably express human PDGFR-beta, we found that arsenite suppressed the angiogenesis mediated by PDGFR-beta. Based on these results, we conclude that arsenite suppressed the angiogenesis of the vascular endothelial cells, that this effect is mediated by PDGFR-beta, and postulate that it might contribute to the injuries of blood vessel in arsenism.
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