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Arsenite suppresses angiogenesis of vascular endothelial cells mediated by Platelet Derived Growth Factor Receptor-beta
Affiliation:1. Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA;2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;3. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Abstract:
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.
Keywords:Arsenic  Angiogenesis  Human umbilical vein endothelial cells  Platelet derived growth factor receptor
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