Effects of Valsartan on Angiotensin II-induced Secretion of tPA and PAI-1 Antigens in Cultured Human Umbilical Vein Endothelial Cells

Objective:To investigate the effects of valsartan on angiotensin Ⅱ(AngⅡ)induced secretion of antigens to tissue type plasminogen activator(tPA) and plasminogen activator inhibitor-1(PAI-1) in cultured human umbilical vein endothelial cells(HUVECs).Methods:HUVECs were collected by enzyme digestion and incubated for 12 hours in the presence of AngⅡ at different concentrations(10-9~10-6mol/L).The cells with 10-7mol/L AngⅡ were incubated for different periods(0,2,6,12,24 and 48 h).Cultured HUVECs were incubated for 12 hours in the presence of 10-7mol/L AngⅡ in combination with valsartan at different concentrations(10-8~10-5mol/L).Cultured HUVECs were incubated for 12 hours in the presence of 10-6mol/L valsartan.Antigens of tPA and PAI-1 were quantified by enzyme-linked immunosorbent assay.Results:AngⅡ induced a time and concentration-dependent increase of PAI-1 antigen,which reached a plateau after 12 hours of incubation with 10-7mol/L AngⅡ [(198.08±7.85)ng/mL vs(22.93±4.73) ng/mL,P0.01].The AngⅡ-induced PAI-1 antigen was inhibited,in a concentration-dependent manner,by valsartan.The effect of 10-6mol/L valsartan was the most significant [(164.73±5.36)ng/mL vs(211.00±9.34) ng/mL,P0.01].Both AngⅡ and valsartan did not interfere with the secretion of tPA antigen.Conclusions:AngⅡ impairs the fibrinolytic potential of HUVECs by increasing the synthesis of PAI-1.This effect is reversed by valsartan,suggesting that angiotensin Ⅱ receptor blockers contributes to the prevention and therapy of atherosclerotic and thrombotic diseases.