EFFECT OF HEAT-SHOCK ON THE EXPRESSION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR RECEPTOR IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

We investigated the effect of heat shock on the fibrinolytic potential of human umbilical vein endothelial cells (HUVECs) in culture. When c ultured at 43 degrees C, the mRNA for heat shock protein 70 (HSP70) wa s dramatically induced within 120 min with a maximal induction of more than 90-fold compared with that in HUVECs cultured at 37 degrees C. T he level of urokinase-type plasminogen activator (u-PA) receptor (u-PA R) mRNA increased up to 2.2-fold in response to heat shock, which was associated with the increased u-PA binding and cell-surface u-PA activ ity determined by adding exogenous u-PA to acid-treated HUVECs. The in creased u-PAR mRNA returned to normal level when HUVECs were further i ncubated at 37 degrees C for 180 min. and this decline was not affecte d in the presence of actinomycin D. Though the secreted antigens for t issue-type plasminogen activator (t-PA) and type 1 plasminogen activat or inhibitor (PAI-I) in the conditioned medium (CM) of HUVECs were sim ultaneously increased at 43 degrees C during this period, the increase in the levels oft-PA (about 26.6-fold at 120 min) was greater than th at of PAI-I (1.8-fold at 120 min), The fibrinolytic activity of CM obt ained from HUVECs at 43 degrees C was significantly enhanced up to 3-f old, indicating that heat shock induced hyperfibrinolytic states in HU VECs. The secretion of u-PA into CM was also enhanced by heat shock. T hese results suggested that human endothelial cells respond to hyperth ermia by inducing HSP70 followed by hyperfibrinolytic states with the enhanced expression of u-PAR as well as that of t-PA and u-PA.