Although in-vivo exposure of PM2.5 has been suggested to initiate a disorder on vascular permeability, the effects and related mechanism has not been well defined. In this work, an obvious increase on vascular permeability has been confirmed in vivo by vein injection of PM2.5 into Balb/c mouse. Human umbilical vein vascular endothelial cells and the consisted ex-vivo vascular endothelium were used as model to investigate the effects of PM2.5 on the vascular permeability and the underlying molecular mechanism. Upon PM2.5 exposure, the vascular endothelial growth factor receptor 2 on cell membrane phosphorylates and activates the downstream mitogen-activated protein kinase (MAPK)/ERK signaling. The adherens junction protein VE-cadherin sheds and the intercellular junction opens, damaging the integrity of vascular endothelium via paracellular pathway. Besides, PM2.5 induces the intracellular reactive oxygen species (ROS) production and triggers the oxidative stress including activity decrease of superoxide dismutase, lactate dehydrogenase release and permeability increase of cell membrane. Taken together, the paracellular and transcellular permeability enhancement jointly contributes to the significant increase of endothelium permeability and thus vascular permeability upon PM2.5 exposure. This work provides an insight into molecular mechanism of PM2.5 associated cardiovascular disease and offered a real-time screening method for the health risk of PM2.5.
Keywords: Fine particulate matter (PM(2.5)); Mitogen-activated protein kinase signaling; Oxidative stress; Vascular endothelial growth factor receptor; Vascular permeability.
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