Effect of AP-1 on expression of plasminogen activator inhibitor-1 in human vascular endothelial cells / 中国医学科学院学报

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of nuclear transcription factor AP-1 on tumor necrosis factor alpha (TNF-alpha) or minimal modified low density lipoprotein (mmLDL)-induced expression of plasminogen activator inhibitor-1 (PAI-1) in human vascular endothelial cells.</p><p><b>METHODS</b>Using gene recombination techniques, four luciferase reporter gene plasmids containing different length of human PAI-1 gene promoter were constructed. Through the transient transfection analysis, the roles of AP-1 element (from -823 bp to -553 bp) in PAI-1 promoter have been determined. In order to further verify the role of AP-1 element, the three site-directed mutants were recovered using PCR and sequencing assay.</p><p><b>RESULTS</b>The induction by TNF-alpha or mmLDL were decreased markedly when the three AP-1 elements in PAI-1 promoter had been mutated respectively.</p><p><b>CONCLUSIONS</b>These results indicate that the AP-1 element in PAI-1 promoter may have important role in PAI-1 gene transcriptions in endothelial cells induced by TNF-alpha or mmLDL.</p>