Effects Of Bisphenol A On The Permeability Of Endothelial Cells And Study Of Some Related Mechanisms

Objective: Bisphenol A is recognized as one of environmental endocrine disruptors,which has potential harm on cardiovascular system,but there is little research about it.Abnormal vascular permeability is closely related to the occurrence of cardiovascular diseases.To observe the effects of BPA on permeability of vascular endothelial cells and explore some related mechanisms.Methods: Bovine aortic endothelial cells were cultured in vitro,exposure to different doses of bisphenol A(1nmol/L-100?mol/L)and pretreating with PKI which was a specific inhibitor of the extracellular signal regulated kinase PKA(10?mol/L).CCK-8 detection kit was used to check the viability of endothelial cell;the protein expression of VE-cadherin and Cav-1 were determined by Western Blot;the expression of VE-cadherin and Cav-1 in endothelial cells were detected by Immunofluorescence;the mRNA expression of VE-cadherin,ZO-1,Claudin-5 and Cav-1 were detected by RT-PCR.Results:(1)The viability of endothelial cells was significantly decreased after treatment of 100?mol/L BPA(P<0.05)while no effects were observed under the other concentrations(P>0.05).(2)0.01?mol/L,0.1?mol/L and 10?mol/L BPA increased the permeability of endothelial cells(P<0.05),and the increase of 0.1?mol/L was the most obvious.PKI pretreatment could further increase the permeability of endothelial cells induced by BPA(P<0.05).(3)There was no effect on the protein expression of VE-cadherin no matter which dose of BPA intervened vascular endothelial cells(P>0.05),while 0.1?mol/L BPA could decrease the mRNA expression of VE-cadherin,ZO-1 and Claudin-5(P<0.05).(4)low concentration of BPA could up regulate the expression of Cav-1 protein and mRNA in endothelial cells(P<0.05),and PKI could further increased the expression induced by BPA(P<0.05).Conclusions: BPA under the concentration of 0.01?mol/L,0.1?mol/L and 10?mol/L could increase the permeability of endothelial cells,but the intercellular connections were not destroyed.The alterative expression of Cav-1 suggested that BPA increased cellular permeability through caveolae which mediated substrates transportation across membranes.PKA signaling pathway was involved in increase of permeability of endothelial cells induced by BPA and might protect the endothelial cells by reducing the transport of caveolae.