Effects of native, triglyceride-enriched, and oxidatively modified LDL on plasminogen activator inhibitor-1 expression in human endothelial cells

Whereas VLDL has consistently been shown to induce a concentration-dependen t increase in the expression of plasminogen activator inhibitor-1 (PAI-1) i n human umbilical vein endothelial cells (HUVECs) and liver cells, variable effects have been reported for native and oxidatively modified LDL. In the :present study, activation of PAI-1 protein and mRNA expression by native L DL (nLDL), UV-oxidized LDL (uvLDL), and triglyceride (TG)-enriched LDL was studied in HUVECs by using different incubation times and a wide range of l ipoprotein concentrations. No significant increase of PAI-1-protein express ion was observed after 4 hours of incubation with nLDL or uvLDL. However, P AI-1 protein secretion from HUVECs was markedly enhanced after 18 hours of incubation with uvLDL (200% increase at 10 mu g/mL). Stimulation of PAI-1 p rotein expression in HUVECs by nLDL was seen, however, after increasing the TG content of the LDL particle. LDL enriched in phospholipid had no effect on PAI-1 secretion. PAI-1 mRNA levels on northern blot increased in parall el with the activation of PAI-1 protein expression by native and modified f orms of LDL. Low concentrations of TG-enriched LDL (10 mu g/mL) and higher concentrations of nLDL and uvLDL (100 mu g/mL) were found to increase the b inding of a VLDL-inducible transcription factor to the PAI-I promoter. Thes e results indicate that the TG content of the LDL particle influences PAI-1 expression in endothelial cells; Low concentrations of uvLDL enhanced PAI- 1 protein and mRNA expression in the HUVECs after an 18-hour incubation but did not influence the VLDL-inducible transcription factor. This suggests t hat low levels of oxidized LDL increase PAI-1 expression by a different mec hanism than VLDL and TG-enriched LDL.