Effects And Mechanisms Of Arsenic Species On The Angiogenesis Of Human Umbilical Vein Endothelial Cells

Effects of arsenic species of NaAsO2, Na3AsO4and Roxarsone on theproliferation, migration and angiogenesis of human umbilical vein endothelial cells(HUVEC) were investigated, and the molecular mechanisms of NaAsO2modulationto angiogenesis were explored also. Experimental parts and main results of this studywere shown as following:1. The HUVEC cultures were treated with arsenic species of NaAsO2, Na3AsO4,and Roxarsone for48h at0-5μM,0-40μM, and0-80μM, respectively. Thedose-dependent effect of arsenic species on cells proliferation was detected by MTTassay. At indicated dosages and time points, the changes of cell cycle were monitoredby flow cytometry analysis, the cells migration was measured by in vitro scratch assaymethod, and the angiogenesis of HUVEC was determined by in vitro angiogenesisassay on the extracellular matrix gel. We found that treatments of NaAsO2at0.25-1μM induced significant increases in proliferation and angiogenesis of HUEVCs,while slightly changes in cells proliferation, migration, and angiogenesis weredetected with treatments of Na3AsO4and Roxarsone at the present dosages.2. Furthermore, we found a dual-effect of NaAsO2on NO production, NOSactivity, ROS generation and Ca2+flux in HUVEC. Treatments of NaAsO2at0.25-1μM caused up-regulated, while treatments at2.5-5μM resulted indown-regulated NO secretion and NOS activities. Additionally, compared with thenon-treated control, cells treated with0.25-1μM of NaAsO2were shown significantlower ROS generation followed with increased Ca2+flux and angiogenesis, but cellswith NaAsO2treatments at2.5-5μM displayed higher ROS generation followed withdecreased Ca2+flux and angiogenesis.In conclusion, our data indicated that the effects of arsenic on HUVECproliferation, migration and angiogenesis were speciation-and/or dose-dependent.The dual biological impacts of NaAsO2on HUEVC suggested that tissue proliferationmight be promoted by low arsenic exposure, but inhibited by high arsenic exposure. The NO secretion, NOS activity, ROS generation and calcium homeostasis involvedin the molecular mechanisms of bio-modulation of arsenicals.