The Suppressive Effects Of Arsenite On The Angiogenesis Of Vascular Endothelial Cells And The Molecular Mechanisms Involved

Arsenic disease by drinking water has become the major threat to human health,and peripheral vascular is the main target organ, endothelial cels play a key role in the process of vascular integrity maintenance and repairment of damaged blood vessels regulated by various cytokines and their corresponding tyrosine kinases(TRK)receptors in the process of the role of receptor. Studies have confirmed that arsenite can inhibit proliferation and apoptosis in endothelial cells, but the mechanism of arsenite on endothelial cell tube formation in vitro is still a lack of systematic research.The present study was aimed at investigating the relationship between the effects of endothelial cells angiogenesis caused by arsenite and its molecular mechanism. First,the angiogenic ability to form tubular networks of HUVECS was analyzed by 2D metrigel in vitro angiogenesis assay to explore the effects of capillary tube formation ability caused by arsenite, and then studied the effects of more targets tyrosine kinase inhibitors E7080 and specific PDGFR beta tyrosine kinase inhibitor CP- 673451 on endothelial cells angiogenesis progress. Finally we adopted PDGFR mediated endothelial cells(PDGFRβ/ PAE cells) to explore the role of PDGFRβin the vitro angiogenesis more visually and explored the effects of capillary tube formation ability of PDGFRβ/PAE cells caused by sodium arsenite.The results show that sodium arsenite inhibits the tubule formation of HUVECS and there are time-response and dose-effect relationships, as the dose increased, the inhibition increased gradually, under the effect of the same concentration with time prolonging, inhibit rate increased gradually;PDGFBB / PDGFRβsignaling pathways play a important role in HUVECS vitro angiogenesis process mediated by receptor tyrosine kinase In purification of stable expression of PDGFR beta PAE cell lines,sodium arsenite inhibiting the tube formation capacity of PAE cells and there are timeresponse and dose effect relationships in our study concentration range. These results provide a new theoretical evidence on that function injury of blood vessel caused by arsenide and the molecular mechanism included. it makes perfect sense for pathogenesis and prevention of injuries of blood vessel in arsenism.