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

被引:44
作者
Allison, BA [1 ]
Nilsson, L [1 ]
Karpe, F [1 ]
Hamsten, A [1 ]
Eriksson, P [1 ]
机构
[1] Karolinska Hosp, Karolinska Inst, Dept Med, King Gustaf V Res Inst,Atherosclerosis Res Unit, S-17176 Stockholm, Sweden
关键词
plasminogen activator inhibitor-1; LDL; oxidized LDL; triglycerides;
D O I
10.1161/01.ATV.19.5.1354
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Whereas VLDL has consistently been shown to induce a concentration-dependent increase in the expression of plasminogen activator inhibitor-1 (PAI-1) in 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 LDL (nLDL), UV-oxidized LDL (uvLDL), and triglyceride (TG)-enriched LDL was studied in HUVECs by using different incubation times and a wide range of lipoprotein concentrations. No significant increase of PAI-1-protein expression was observed after 4 hours of incubation with nLDL or uvLDL. However, PAI-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 protein 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 parallel with the activation of PAI-1 protein expression by native and modified forms 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 binding of a VLDL-inducible transcription factor to the PAI-I promoter. These 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 that low levels of oxidized LDL increase PAI-1 expression by a different mechanism than VLDL and TG-enriched LDL.
引用
收藏
页码:1354 / 1360
页数:7
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