An elevated plasma cholesterol level has been shown to be a risk factor in the development of atherosclerosis and coronary heart disease. Low density lipoproteins (LDL) are the major carriers of cholesterol in the blood and many cells carry receptors for LDL on their surface. However, LDL does not appear to injure endothelial cells in vitro. Abnormal triglyceride rich lipoproteins (very low density lipoproteins, VLDL) from hypertriglyceridemic (HTG) patients have been shown to injure endothelial cells and receptors for HTG VLDL have been detected on endothelial cells. We have initiated a study to determine the changes in mRNA synthesis of key fibrinolytic and coagulation proteins in HUVEC after exposure of the cells to various lipoproteins from normal individuals as well as from patients with HTG to determine if lipoproteins affect the normal hemostatic mechanism on endothelial cells. Lipoprotein fractions were obtained from Dr. Richard Muesing and incubated with HUVEC for a 4 hr period. The cells were then processed to obtain the RNA which is hybridized with probes specific for the fibrinolytic system proteins (t-PA, u-PA, and PAI-1). Future studies will include a probe for tissue factor, a coagulation system protein. Control samples included cells treated with thrombin and I1-1 which are known to increase synthesis of these proteins. Preliminary results indicate that LDL increase levels of mRNA for the fibrinolytic proteins (t-PA, u-PA, and PAI-1) whereas VLDL do not. Further work is continuing to determine whether these changes are significant.
