Influence of Hyperthermia on the Fibrinolytic Potential of Human Endothelial Cells

Abstract

The effect of exposure to hyperthermia on the fibrinolytic potential of human umbilical vein endothelial cells (HUVEC) in culture was studied. HUVEC responded to exposure to 42°C with a time dependent increase in plasminogen activator inhibitor type 1 (PAI-1) activity and antigen and a decrease in tissue-type plasminogen activator (t-PA) antigen. Hyperthermic treatment did not influence cell viability as judged by 51Cr release. The effect of short term exposure to hyperthermia on PAI-1 activity and antigen could not be reversed by reexposure of the cells to 37°C for 24 hours as evidenced by continuously increased amounts of PAI-1 released into the conditioned media. t-PA release, however, increased significantly over control in the 24 hours at 37°following short term exposure to hyperthermia. No difference in PAI-1 antigen present in the extracellular matrix of heat treated HUVEC as compared to HUVEC kept at 37° could be found. Furthermore it could be demonstrated by Northern blotting techniques that hyperthermia induced the increase in PAI-1 by increased synthesis as evident by the presence of elevated m-RNA levels. Our data supports the idea that hyperthermia is one stress factor influencing the fibrinolytic potential of endothelial cells.